42 results on '"Gückel B"'
Search Results
2. MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-κB and TGF-β signaling pathways
- Author
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Keklikoglou, I, Koerner, C, Schmidt, C, Zhang, J D, Heckmann, D, Shavinskaya, A, Allgayer, H, Gückel, B, Fehm, T, Schneeweiss, A, Sahin, Ö, Wiemann, S, and Tschulena, U
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- 2012
- Full Text
- View/download PDF
3. Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course
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Koh, Dow-Mu, Kaste, Sue Creviston, Vinnicombe, Sarah J., Morana, Giovanni, Rossi, Andrea, Herold, Christian J., McLoud, Theresa C., Frey, Kirk A., Gebauer, Bernhard, Roebuck, Derek, Fütterer, Jurgen J., Towbin, Alexander J., Huisman, Thierry A. G., Smets, Anne M. J. B., Lee, Jeong Min, Chandarana, Hersh, Mayerhoefer, Marius E., Raderer, Markus, Haug, Alexander, Eiber, Matthias, Rockall, Andrea, Sohaib, Aslam, Warbey, Victoria S, Vargas, Hebert Alberto, Heiken, Jay P., Francis, Isaac R., Al-Hawary, Mahmoud M., Kaza, Ravi K., D’Onofrio, Mirko, Thoeny, Harriet C., King, Ann D., Piccardo, Arnoldo, Garrè, Maria Luisa, Reed, Nick, Rodriguez-Galindo, Carlos, Wasnik, Ashish P., Diederich, Stefan, Oyen, Wim J. G., Chaw, Cheng Lee, van As, Nicholas, Vieira, Igor, De Keyzer, Frederik, Dresen, Elleke, Han, Sileny, Vergote, Ignace, Moerman, Philippe, Amant, Frederic, Koole, Michel, Vandecaveye, Vincent, Dresen, R., De Vuysere, S., De Keyzer, F., Van Cutsem, E., D’Hoore, A., Wolthuis, A., Vandecaveye, V., Pricolo, P., Alessi, S., Summers, P., Tagliabue, E., Petralia, G., Pfannenberg, C., Gückel, B., Schüle, S. C., Müller, A. C., Kaufmann, S., Schwenzer, N., Reimold, M., la Fougere, C., Nikolaou, K., Martus, P., Cook, G. J., Azad, G. K., Taylor, B. P., Siddique, M., John, J., Mansi, J., Harries, M., Goh, V., Seth, S., Burgul, R., Seth, A., Waugh, S., Gowdh, N. Muhammad, Purdie, C., Evans, A., Crowe, E., Thompson, A., Vinnicombe, S., Arfeen, F., Campion, T., Goldstraw, E., D’Onofrio, M., Ciaravino, V., Crosara, S., De Robertis, R., Mucelli, R. Pozzi, Uhrig, M., Simons, D., Schlemmer, H., Downey, Kate, Murdoch, S., Al-adhami, A. S., Viswanathan, S., Smith, S., Jennings, P., Bowers, D., Soomal, R., Mutala, T. M., Odhiambo, A. O., Harish, N., Hall, M., Sproule, M., Sheridan, S., Thein, K. Y., Tan, C. H., Thian, Y. L., Ho, C. M., De Luca, S., Carrera, C., Blanchet, V., Alarcón, L., Eyheremnedy, E., Choudhury, B. K., Bujarbarua, K., Barman, G., Lovat, E., Ferner, R., Warbey, V. S., Potti, L., Kaye, B., Beattie, A., Dutton, K., Seth, A. A., Constantinidis, F., Dobson, H., Bradley, R., Bozas, G., Avery, G., Stephens, A., Maraveyas, A., Bhuva, S., Johnson, C. A., Subesinghe, M., Taylor, N., Quint, L. E., Reddy, R. M., Kalemkerian, G. P., Zapico, G. González, Jauregui, E. Gainza, Francisco, R. Álvarez, Alonso, S. Ibáñez, Bahillo, I. Tavera, Álvarez, L. Múgica, Francies, O., Wheeler, R., Childs, L., Adams, A., Sahdev, A., De Luca, S. E., Vañek, M. E. Casalini, Pascuzzi, M. D., Gillanders, T., Ramos, P. M., Eyheremendy, E. P., Stove, C., Digby, M., Nazar, M., Wirtz, M., Troncoso, F., Saguier, F., Quint, D. J., Dang, L., Carlson, M., Leber, S., Silverstein, F., Rueben, R., Nazir, B., Teo, T. H., Khoo, J. B., Sharma, K., Gupta, N., Mathew, B., Jeyakumar, T., Harkins, K., Joshua, S., Christodoulou, D., Gourtsoyianni, S., Jacques, A., Griffin, N., Lee, J., Goodfellow, J. A., Yong, A., Jenkins, S., Joseph, G., Partington, K., Zanfardini, A., Cavanagh, K., and Lau, E.
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,Radiological and Ultrasound Technology ,Oncology ,Radiology Nuclear Medicine and imaging ,lcsh:R895-920 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Meeting Abstracts ,lcsh:RC254-282 - Abstract
Table of contents O1 Tumour heterogeneity: what does it mean? Dow-Mu Koh O2 Skeletal sequelae in adult survivors of childhood cancer Sue Creviston Kaste O3 Locoregional effects of breast cancer treatment Sarah J Vinnicombe O4 Imaging of cancer therapy-induced CNS toxicity Giovanni Morana, Andrea Rossi O5 Screening for lung cancer Christian J. Herold O6Risk stratification of lung nodules Theresa C. McLoud O7 PET imaging of pulmonary nodules Kirk A Frey O8 Transarterial tumour therapy Bernhard Gebauer O9 Interventional radiology in paediatric oncology Derek Roebuck O10 Image guided prostate interventions Jurgen J. Fütterer O11 Imaging cancer predisposition syndromes Alexander J. Towbin O12Chest and chest wall masses Thierry AG Huisman O13 Abdominal masses: good or bad? Anne MJB Smets O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management Giovanni Morana O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC Jeong Min Lee O16 Opportunities and challenges in imaging metastatic disease Hersh Chandarana O17 Diagnosis, treatment monitoring, and follow-up of lymphoma Marius E. Mayerhoefer, Markus Raderer, Alexander Haug O18 Managing high-risk and advanced prostate cancer Matthias Eiber O19 Immunotherapy: imaging challenges Bernhard Gebauer O20 RECIST and RECIST 1.1 Andrea Rockall O21 Challenges of RECIST in oncology imaging basics for the trainee and novice Aslam Sohaib O22 Lymphoma: PET for interim and end of treatment response assessment: a users’ guide to the Deauville Score Victoria S Warbey O23 Available resources Hebert Alberto Vargas O24 ICIS e-portal and the online learning community Dow-Mu Koh O25 Benign lesions that mimic pancreatic cancer Jay P Heiken O26 Staging and reporting pancreatic malignancies Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza O27 Intraductal papillary mucinous neoplasm Giovanni Morana O28 Cystic pancreatic tumours Mirko D’Onofrio O29 Diffusion-weighted imaging of head and neck tumours Harriet C. Thoeny O30 Radiation injury in the head and neck Ann D King O31 PET/MR of paediatric brain tumours Giovanni Morana, Arnoldo Piccardo, Maria Luisa Garrè, Andrea Rossi O32 Structured reporting and beyond Hebert Alberto Vargas O33 Massachusetts General Hospital experience with structured reporting Theresa C. McLoud O34 The oncologist’s perspective: what the oncologist needs to know Nick Reed O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology Carlos Rodriguez-Galindo O36 Multiparametric imaging of renal cancers Hersh Chandarana O37 Linking imaging features of renal disease and their impact on management strategies Hebert Alberto Vargas O38 Adrenals, retroperitoneum and peritoneum Isaac R Francis, Ashish P Wasnik O39 Lung and pleura Stefan Diederich O40 Advances in MRI Jurgen J. Fütterer O41 Advances in molecular imaging Wim J.G. Oyen O42 Incorporating advanced imaging, impact on treatment selection and patient outcome Cheng Lee Chaw, Nicholas van As S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A D’Hoore, A Wolthuis, V Vandecaveye S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer. P. Pricolo (paola.pricolo@ieo.it), S. Alessi, P. Summers, E. Tagliabue, G. Petralia S4 Generating evidence for clinical benefit of PET/CT – are management studies sufficient as surrogate for patient outcome? C. Pfannenberg, B. Gückel, SC Schüle, AC Müller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh S6 Accuracy of suspicious breast imaging—can we tell the patient? S Seth, R Burgul, A Seth S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe S8 Diagnostic yield of CT IVU in haematuria screening F. Arfeen, T. Campion, E. Goldstraw S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results D’Onofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients M. Uhrig, D. Simons, H. Schlemmer S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb? Kate Downey S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield. S Murdoch, AS Al-adhami, S Viswanathan P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations S Smith, P Jennings, D Bowers, R Soomal P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease S Smith, P Jennings, D Bowers, R Soomal P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges TM Mutala, AO Odhiambo, N Harish P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015 M. Hall, M. Sproule, S. Sheridan P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm KY Thein, CH Tan, YL Thian, CM Ho P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience S De Luca, C Carrera, V Blanchet, L Alarcón, E Eyheremnedy P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25 years experience B K Choudhury, K Bujarbarua, G Barman P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions L Potti, B Kaye, A Beattie, K Dutton P11 Can we reduce prevalent recall rate in breast screening? AA Seth, F Constantinidis, H Dobson P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV) AA Seth (archana.seth@nhs.net), F Constantinidis, H Dobson P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas P14 A one-stop lymphoma biopsy service – is it possible? S Bhuva, CA Johnson, M Subesinghe, N Taylor P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017) LE Quint, RM Reddy, GP Kalemkerian P16 Cancer immunotherapy: a review of adequate imaging assessment G González Zapico, E Gainza Jauregui, R Álvarez Francisco, S Ibáñez Alonso, I Tavera Bahillo, L Múgica Álvarez P17 Succinate dehydrogenase mutations and their associated tumours O Francies, R Wheeler, L Childs, A Adams, A Sahdev P18 Initial experience in the usefulness of dual energy technique in the abdomen SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy P19 Recognising the serious complication of Richter’s transformation in CLL patients C Stove, M Digby P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein P22 Pitfalls in oncology CT reporting. A pictorial review R Rueben, S Viswanathan P23 Imaging of perineural extension in head and neck tumours B Nazir, TH Teo, JB Khoo P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins P25 When cancer can’t wait! A pictorial review of oncological emergencies K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh P27 Gynaecological cancers in pregnancy: a review of imaging CA Johnson, J Lee P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart JA Goodfellow, AS Al-adhami, S Viswanathan P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy R Bradley P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience R Bradley P31 Radiological assessment of the post-chemotherapy liver A Yong, S Jenkins, G Joseph P32 Skeletal staging with MRI in breast cancer – what the radiologist needs to know S Bhuva, K Partington P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease CA Johnson, S Bhuva, M Subesinghe, N Taylor P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools. C Carrera, A Zanfardini, S De Luca, L Alarcón, V Blanchet, EP Eyheremendy P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test? K Cavanagh, E Lau
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- 2016
4. Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen
- Author
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Bailey, D. L., Pichler, B. J., Gückel, B., Antoch, G., Barthel, H., Bhujwalla, Z. M., Biskup, S., Biswal, S., Bitzer, M., Boellaard, R., Braren, R. F., Brendle, C., Brindle, K., Chiti, A., La Fougère, C., Gillies, R., Goh, V., Goyen, M., Hacker, M., Heukamp, L., Knudsen, G. M., Krackhardt, A. M., Law, I., Morris, J. C., Nikolaou, K., Nuyts, J., Ordonez, A. A., Pantel, K., Quick, H. H., Riklund, K., Sabri, O., Sattler, B., Troost, E., Zaiss, M., Zender, L., and Beyer, T.
- Abstract
The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.
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- 2018
5. Combined PET/MRI:Global Warming - Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany
- Author
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Bailey, D L, Pichler, B J, Gückel, B, Antoch, G, Barthel, H, Bhujwalla, Z M, Biskup, S, Biswal, S, Bitzer, M, Boellaard, R, Braren, R F, Brendle, C, Brindle, K, Chiti, A, la Fougère, C, Gillies, R, Goh, V, Goyen, M, Hacker, M, Heukamp, L, Knudsen, G. M., Krackhardt, A M, Law, I., Morris, J C, Nikolaou, K, Nuyts, J, Ordonez, A A, Pantel, K, Quick, H H, Riklund, K, Sabri, O, Sattler, B, Troost, E G C, Zaiss, M, Zender, L, Beyer, Thomas, Bailey, D L, Pichler, B J, Gückel, B, Antoch, G, Barthel, H, Bhujwalla, Z M, Biskup, S, Biswal, S, Bitzer, M, Boellaard, R, Braren, R F, Brendle, C, Brindle, K, Chiti, A, la Fougère, C, Gillies, R, Goh, V, Goyen, M, Hacker, M, Heukamp, L, Knudsen, G. M., Krackhardt, A M, Law, I., Morris, J C, Nikolaou, K, Nuyts, J, Ordonez, A A, Pantel, K, Quick, H H, Riklund, K, Sabri, O, Sattler, B, Troost, E G C, Zaiss, M, Zender, L, and Beyer, Thomas
- Abstract
The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we
- Published
- 2018
6. Combined PET/MRI:Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany
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Bailey, D. L., Pichler, B. J., Gückel, B., Barthel, H., Beer, A. J., Bremerich, J., Czernin, J., Drzezga, A., Franzius, C., Goh, V., Hartenbach, M., Iida, H., Kjaer, Andreas, la Fougère, C., Ladefoged, C. N., Law, I., Nikolaou, K., Quick, H. H., Sabri, O., Schäfer, J., Schäfers, M., Wehrl, H. F., Beyer, T., Bailey, D. L., Pichler, B. J., Gückel, B., Barthel, H., Beer, A. J., Bremerich, J., Czernin, J., Drzezga, A., Franzius, C., Goh, V., Hartenbach, M., Iida, H., Kjaer, Andreas, la Fougère, C., Ladefoged, C. N., Law, I., Nikolaou, K., Quick, H. H., Sabri, O., Schäfer, J., Schäfers, M., Wehrl, H. F., and Beyer, T.
- Abstract
This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.
- Published
- 2015
7. Combined PET/MR: Where Are We Now? Summary Report of the Second International Workshop on PET/MR Imaging April 8–12, 2013, Tubingen, Germany
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Bailey, D. L., Barthel, H., Beuthien-Baumann, B., Beyer, T., Bisdas, S., Boellaard, R., Czernin, J., Drzezga, A., Ernemann, U., Franzius, C., Gückel, B., Handgretinger, R., Hartenbach, M., Hellwig, D., Nadel, H., Nekolla, S. G., Pfluger, T., Pichler, B. J., Quick, H. H., Sabri, O., Sattler, B., Schäfer, J., Schick, F., Siegel, B. A., Schlemmer, H. P., Schwenzer, N. F., Hoff, J., Veit-Haibach, P., Wehrl, H. F., Bailey, D. L., Barthel, H., Beuthien-Baumann, B., Beyer, T., Bisdas, S., Boellaard, R., Czernin, J., Drzezga, A., Ernemann, U., Franzius, C., Gückel, B., Handgretinger, R., Hartenbach, M., Hellwig, D., Nadel, H., Nekolla, S. G., Pfluger, T., Pichler, B. J., Quick, H. H., Sabri, O., Sattler, B., Schäfer, J., Schick, F., Siegel, B. A., Schlemmer, H. P., Schwenzer, N. F., Hoff, J., Veit-Haibach, P., and Wehrl, H. F.
- Abstract
This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.
- Published
- 2014
8. Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity
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Lindauer, M, Rudy, W, Gückel, B, Doeberitz, M V, Meuer, S C, and Moebius, U
- Subjects
HLA-DR3 Antigen ,B7-1 Antigen ,Gene Transfer Techniques ,Gene Expression ,Humans ,hemic and immune systems ,chemical and pharmacologic phenomena ,CD8-Positive T-Lymphocytes ,Colorectal Neoplasms ,Intercellular Adhesion Molecule-1 ,Lymphocyte Activation ,Cell Division ,Research Article - Abstract
Colorectal cancer is considered a non-immunogenic malignany. One strategy to augment the immunogenicity of such tumours is represented by the expression of costimulatory molecules by gene transfer. Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells. This demonstrates that the generation of immunogenic tumour cell variants, i.e. for the use as cellular vaccines, requires multiple genetic alterations in the case of non-immunogenic human tumours cells, such as colorectal cancer cells.
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- 1998
9. MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-κB and TGF-β signaling pathways
- Author
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Keklikoglou, I, primary, Koerner, C, additional, Schmidt, C, additional, Zhang, J D, additional, Heckmann, D, additional, Shavinskaya, A, additional, Allgayer, H, additional, Gückel, B, additional, Fehm, T, additional, Schneeweiss, A, additional, Sahin, Ö, additional, Wiemann, S, additional, and Tschulena, U, additional
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- 2011
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10. Entwicklung einer Peptid-basierten Vakzine gegen Antigene des Ovarialkarzinoms (OvCa) und dessen tumorassoziiertem Endothel – Präklinische Studie
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Hörzer, H, primary, Marmé, A, additional, Stevanovic, S, additional, Altevogt, P, additional, Wallwiener, D, additional, and Gückel, B, additional
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- 2008
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11. Vakzinierungen mit peptidbeladenen Dendritischen Zellen (DC) führen zur Aktivierung Tumorantigen-spezifischer Immunreaktionen – Phase-I/II-Studie für met. Brustkrebspatientinnen
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Gückel, B, primary, Kayser, S, additional, Gruber, I, additional, Waidmann, M, additional, Wallwiener, D, additional, and Marmé, A, additional
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- 2008
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12. Allogene Vakzine auf Basis einer CD80-modifizierten, immunkompetenten Mammakarzinom-Zellinie: erste klinische Ergebnisse – Phase I-Studie für met. Brustkrebspatientinnen
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Gückel, B, primary, Kayser, S, additional, Gruber, I, additional, Wallwiener, D, additional, Meuer, S, additional, and Marmé, A, additional
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- 2008
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13. Zelluläre Immuntherapie: Ein neuer Ansatz in der Therapie des Mammakarzinoms
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Schütz, F., primary and Gückel, B., additional
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- 2007
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14. DC/Peptid-Vakzinierung für Mammakarzinom (MaCa)-Patientinnen mit „low risk“-Metastasierungsmuster
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Gückel, B, primary, Kayser, S, additional, Gruber, I, additional, Waidmann, M, additional, Wallwiener, D, additional, and Marmé, A, additional
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- 2006
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15. Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course: Glasgow, UK. 3–5 October 2016
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Koh, Dow-Mu, Kaste, Sue Creviston, Vinnicombe, Sarah J., Morana, Giovanni, Rossi, Andrea, Herold, Christian J., McLoud, Theresa C., Frey, Kirk A., Gebauer, Bernhard, Roebuck, Derek, Fütterer, Jurgen J., Towbin, Alexander J., Huisman, Thierry A. G., Smets, Anne M. J. B., Lee, Jeong Min, Chandarana, Hersh, Mayerhoefer, Marius E., Raderer, Markus, Haug, Alexander, Eiber, Matthias, Rockall, Andrea, Sohaib, Aslam, Warbey, Victoria S, Vargas, Hebert Alberto, Heiken, Jay P., Francis, Isaac R., Al-Hawary, Mahmoud M., Kaza, Ravi K., D’Onofrio, Mirko, Thoeny, Harriet C., King, Ann D., Piccardo, Arnoldo, Garrè, Maria Luisa, Reed, Nick, Rodriguez-Galindo, Carlos, Wasnik, Ashish P., Diederich, Stefan, Oyen, Wim J. G., Chaw, Cheng Lee, van As, Nicholas, Vieira, Igor, De Keyzer, Frederik, Dresen, Elleke, Han, Sileny, Vergote, Ignace, Moerman, Philippe, Amant, Frederic, Koole, Michel, Vandecaveye, Vincent, Dresen, R., De Vuysere, S., De Keyzer, F., Van Cutsem, E., D’Hoore, A., Wolthuis, A., Vandecaveye, V., Pricolo, P., Alessi, S., Summers, P., Tagliabue, E., Petralia, G., Pfannenberg, C., Gückel, B., Schüle, S. C., Müller, A. C., Kaufmann, S., Schwenzer, N., Reimold, M., la Fougere, C., Nikolaou, K., Martus, P., Cook, G. J., Azad, G. K., Taylor, B. P., Siddique, M., John, J., Mansi, J., Harries, M., Goh, V., Seth, S., Burgul, R., Seth, A., Waugh, S., Gowdh, N. Muhammad, Purdie, C., Evans, A., Crowe, E., Thompson, A., Vinnicombe, S., Arfeen, F., Campion, T., Goldstraw, E., D’Onofrio, M., Ciaravino, V., Crosara, S., De Robertis, R., Mucelli, R. Pozzi, Uhrig, M., Simons, D., Schlemmer, H., Downey, Kate, Murdoch, S., Al-adhami, A. S., Viswanathan, S., Smith, S., Jennings, P., Bowers, D., Soomal, R., Mutala, T. M., Odhiambo, A. O., Harish, N., Hall, M., Sproule, M., Sheridan, S., Thein, K. Y., Tan, C. H., Thian, Y. L., Ho, C. M., De Luca, S., Carrera, C., Blanchet, V., Alarcón, L., Eyheremnedy, E., Choudhury, B. K., Bujarbarua, K., Barman, G., Lovat, E., Ferner, R., Warbey, V. S., Potti, L., Kaye, B., Beattie, A., Dutton, K., Seth, A. A., Constantinidis, F., Dobson, H., Bradley, R., Bozas, G., Avery, G., Stephens, A., Maraveyas, A., Bhuva, S., Johnson, C. A., Subesinghe, M., Taylor, N., Quint, L. E., Reddy, R. M., Kalemkerian, G. P., Zapico, G. González, Jauregui, E. Gainza, Francisco, R. Álvarez, Alonso, S. Ibáñez, Bahillo, I. Tavera, Álvarez, L. Múgica, Francies, O., Wheeler, R., Childs, L., Adams, A., Sahdev, A., De Luca, S. E., Vañek, M. E. Casalini, Pascuzzi, M. D., Gillanders, T., Ramos, P. M., Eyheremendy, E. P., Stove, C., Digby, M., Nazar, M., Wirtz, M., Troncoso, F., Saguier, F., Quint, D. J., Dang, L., Carlson, M., Leber, S., Silverstein, F., Rueben, R., Nazir, B., Teo, T. H., Khoo, J. B., Sharma, K., Gupta, N., Mathew, B., Jeyakumar, T., Harkins, K., Joshua, S., Christodoulou, D., Gourtsoyianni, S., Jacques, A., Griffin, N., Lee, J., Goodfellow, J. A., Yong, A., Jenkins, S., Joseph, G., Partington, K., Zanfardini, A., Cavanagh, K., and Lau, E.
- Abstract
Table of contents O1 Tumour heterogeneity: what does it mean? Dow-Mu Koh O2 Skeletal sequelae in adult survivors of childhood cancer Sue Creviston Kaste O3 Locoregional effects of breast cancer treatment Sarah J Vinnicombe O4 Imaging of cancer therapy-induced CNS toxicity Giovanni Morana, Andrea Rossi O5 Screening for lung cancer Christian J. Herold O6Risk stratification of lung nodules Theresa C. McLoud O7 PET imaging of pulmonary nodules Kirk A Frey O8 Transarterial tumour therapy Bernhard Gebauer O9 Interventional radiology in paediatric oncology Derek Roebuck O10 Image guided prostate interventions Jurgen J. Fütterer O11 Imaging cancer predisposition syndromes Alexander J. Towbin O12Chest and chest wall masses Thierry AG Huisman O13 Abdominal masses: good or bad? Anne MJB Smets O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management Giovanni Morana O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC Jeong Min Lee O16 Opportunities and challenges in imaging metastatic disease Hersh Chandarana O17 Diagnosis, treatment monitoring, and follow-up of lymphoma Marius E. Mayerhoefer, Markus Raderer, Alexander Haug O18 Managing high-risk and advanced prostate cancer Matthias Eiber O19 Immunotherapy: imaging challenges Bernhard Gebauer O20 RECIST and RECIST 1.1 Andrea Rockall O21 Challenges of RECIST in oncology imaging basics for the trainee and novice Aslam Sohaib O22 Lymphoma: PET for interim and end of treatment response assessment: a users’ guide to the Deauville Score Victoria S Warbey O23 Available resources Hebert Alberto Vargas O24 ICIS e-portal and the online learning community Dow-Mu Koh O25 Benign lesions that mimic pancreatic cancer Jay P Heiken O26 Staging and reporting pancreatic malignancies Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza O27 Intraductal papillary mucinous neoplasm Giovanni Morana O28 Cystic pancreatic tumours Mirko D’Onofrio O29 Diffusion-weighted imaging of head and neck tumours Harriet C. Thoeny O30 Radiation injury in the head and neck Ann D King O31 PET/MR of paediatric brain tumours Giovanni Morana, Arnoldo Piccardo, Maria Luisa Garrè, Andrea Rossi O32 Structured reporting and beyond Hebert Alberto Vargas O33 Massachusetts General Hospital experience with structured reporting Theresa C. McLoud O34 The oncologist’s perspective: what the oncologist needs to know Nick Reed O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology Carlos Rodriguez-Galindo O36 Multiparametric imaging of renal cancers Hersh Chandarana O37 Linking imaging features of renal disease and their impact on management strategies Hebert Alberto Vargas O38 Adrenals, retroperitoneum and peritoneum Isaac R Francis, Ashish P Wasnik O39 Lung and pleura Stefan Diederich O40 Advances in MRI Jurgen J. Fütterer O41 Advances in molecular imaging Wim J.G. Oyen O42 Incorporating advanced imaging, impact on treatment selection and patient outcome Cheng Lee Chaw, Nicholas van As S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A D’Hoore, A Wolthuis, V Vandecaveye S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer. P. Pricolo (paola.pricolo@ieo.it), S. Alessi, P. Summers, E. Tagliabue, G. Petralia S4 Generating evidence for clinical benefit of PET/CT – are management studies sufficient as surrogate for patient outcome? C. Pfannenberg, B. Gückel, SC Schüle, AC Müller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh S6 Accuracy of suspicious breast imaging—can we tell the patient? S Seth, R Burgul, A Seth S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe S8 Diagnostic yield of CT IVU in haematuria screening F. Arfeen, T. Campion, E. Goldstraw S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results D’Onofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients M. Uhrig, D. Simons, H. Schlemmer S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb? Kate Downey S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield. S Murdoch, AS Al-adhami, S Viswanathan P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations S Smith, P Jennings, D Bowers, R Soomal P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease S Smith, P Jennings, D Bowers, R Soomal P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges TM Mutala, AO Odhiambo, N Harish P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015 M. Hall, M. Sproule, S. Sheridan P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm KY Thein, CH Tan, YL Thian, CM Ho P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience S De Luca, C Carrera, V Blanchet, L Alarcón, E Eyheremnedy P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25 years experience B K Choudhury, K Bujarbarua, G Barman P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions L Potti, B Kaye, A Beattie, K Dutton P11 Can we reduce prevalent recall rate in breast screening? AA Seth, F Constantinidis, H Dobson P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV) AA Seth (archana.seth@nhs.net), F Constantinidis, H Dobson P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas P14 A one-stop lymphoma biopsy service – is it possible? S Bhuva, CA Johnson, M Subesinghe, N Taylor P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017) LE Quint, RM Reddy, GP Kalemkerian P16 Cancer immunotherapy: a review of adequate imaging assessment G González Zapico, E Gainza Jauregui, R Álvarez Francisco, S Ibáñez Alonso, I Tavera Bahillo, L Múgica Álvarez P17 Succinate dehydrogenase mutations and their associated tumours O Francies, R Wheeler, L Childs, A Adams, A Sahdev P18 Initial experience in the usefulness of dual energy technique in the abdomen SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy P19 Recognising the serious complication of Richter’s transformation in CLL patients C Stove, M Digby P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein P22 Pitfalls in oncology CT reporting. A pictorial review R Rueben, S Viswanathan P23 Imaging of perineural extension in head and neck tumours B Nazir, TH Teo, JB Khoo P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins P25 When cancer can’t wait! A pictorial review of oncological emergencies K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh P27 Gynaecological cancers in pregnancy: a review of imaging CA Johnson, J Lee P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart JA Goodfellow, AS Al-adhami, S Viswanathan P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy R Bradley P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience R Bradley P31 Radiological assessment of the post-chemotherapy liver A Yong, S Jenkins, G Joseph P32 Skeletal staging with MRI in breast cancer – what the radiologist needs to know S Bhuva, K Partington P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease CA Johnson, S Bhuva, M Subesinghe, N Taylor P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools. C Carrera, A Zanfardini, S De Luca, L Alarcón, V Blanchet, EP Eyheremendy P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test? K Cavanagh, E Lau
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- 2016
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16. Anti-CD2 antibodies induce T cell unresponsiveness in vivo.
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Gückel, B, primary, Berek, C, additional, Lutz, M, additional, Altevogt, P, additional, Schirrmacher, V, additional, and Kyewski, B A, additional
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- 1991
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17. Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17–21, 2014, Tübingen, Germany
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Bailey, D. L., Antoch, G., Bartenstein, P., Barthel, H., Beer, A. J., Bisdas, S., Bluemke, D. A., Boellaard, R., Claussen, C. D., Franzius, C., Hacker, M., Hricak, H., la Fougère, C., Gückel, B., Nekolla, S. G., Pichler, B. J., Purz, S., Quick, H. H., Sabri, O., Sattler, B., Schäfer, J., Schmidt, H., van den Hoff, J., Voss, S., Weber, W., Wehrl, H. F., and Beyer, T.
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Hybrid imaging ,Molecular imaging ,PET/CT ,PET/MRI ,PET ,MRI ,Quantification ,Attenuation correction ,Oncology ,Paediatric oncology ,Neurology ,Cardiology - Abstract
This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with “hands-on” tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: “the real work has just started”.
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- 2015
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18. Differential function of CD80- and CD86-transfected human melanoma cells in the presence of IL-12 and IFN-gamma.
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Rudy, W, Gückel, B, Siebels, M, Lindauer, M, Meuer, S C, and Moebius, U
- Abstract
Introduction of co-stimulatory molecules like CD80 and CD86 represents a means to augment the immunogenicity of tumor cells and to induce immune responses directed at tumor antigens. Here we compared CD80- and CD86-transfected human melanoma cells to induce primary immune responses by their capacity to promote proliferation of human allogeneic resting T lymphocytes. CD80- and CD86-transfected SkMel63 melanoma cells induced T cell activation to a comparable degree, which was found to be independent of the cell surface density of these co-stimulatory molecules. Co-expression of CD80 and CD86 did not result in a synergistic increase in T cell proliferation. Both CD80 and CD86 transfectants induced the proliferation of isolated CD4+ or CD8+ T cells. Exogenous IL-2, IL-4 and tumor necrosis factor-alpha respectively enhanced primary T cell proliferation independent of CD80 or CD86 expression. Interestingly, differential activities of CD80 and CD86 were observed following stimulation of resting T cells in the presence of IL-12. Whereas IL-12 increased T cell proliferation in the presence of CD86-transfected melanoma cells, it exhibited an inhibitory function in the presence of CD80-expressing SkMel63 cells. Experimental evidence indicates that this inhibitory effect was mediated by IFN-gamma since (I) IFN-gamma secretion of stimulated T cells was augmented by IL-12, (II) exogenous IFN-gamma also inhibited T cell proliferation induced by CD80- but not CD86-transfected SkMel63 cells and (III) the inhibitory effect of IL-12 was blocked by an anti-IFN-gamma mAb. [ABSTRACT FROM AUTHOR]
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- 1997
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19. Development, monitoring and first immunological results of a phase I/II vaccination trial using genetically modified allogeneic breast cancer cells.
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Gückel, B., Stumm, S., Rentzsch, C., Kayser, S., Gruber, I., Marmé, A., Huober, J., Autschbach, F., Meuer, S., and Wallwiener, D.
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- *
CANCER vaccines , *CANCER cells , *VACCINATION , *IMMUNE response , *T cells - Abstract
The article details the development, monitoring and first immunological results of a vaccination trial using genetically modified allogeneic breast cancer cells. It correlates vaccine-induced immune responses with clinical responses. The article evaluates KS24.22-associated and tumor associated antigens (TAA)-specific T cells with a combination of molecular and cellular immunodiagnostic tests.
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- 2004
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20. Differential genexpression in breast-cancer cell lines following treatment with paclitaxel
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Boschke, Claudia-Barbara and Gückel, B. (Privatdozentin Dr. )
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Breast cancer , Gene expression , Chemotherapy , Taxol ,Differentielle Genexpression , Brustkrebs , Chemotherapie , Taxol - Abstract
Das Mammakarzinom ist mit über einer Million Neuerkrankungen pro Jahr weltweit die häufigste bösartige Tumorerkrankung der Frau. Die chemotherapeutische Behandlung des Mammakarzinoms stellt ein langjährig angewandtes Verfahren dar, das durch klinische und experimentelle Forschung stetigem Wandel unterlegen ist. Paclitaxel, ein Vertreter der Taxane, ist eine der vielversprechendsten Anti-tumorsubstanzen in der gynäkologischen Onkologie. Ziel der vorliegenden Arbeit war es, differentiell exprimierte Gene zwischen unbehandelten und chemotherapeutisch behandelten Mammakarzinom – Zelllinien zu finden. Somit gewonnene Daten lassen neue Erkenntnisse über Wirkungsweisen von Chemotherapeutika u.a. der Apoptose-Induktion zu. Diese Erkenntnisse können in vielerlei Hinsicht relevant sein. Es ließen sich zum Beispiel neue Kombinationstherapien entwickeln, die sich dann auch bezügliche ihrer molekularbiologischen Wirkungsweisen ergänzen. Durch den Vergleich der Genexpression mit dem Verfahren des Differential Display und der subtraktiven Hybridisierung gelang es, unter anderem, als differentiell exprimiertes Gen, das Insulin-like Growth Factor Binding Protein–5 (IGFBP-5) zu identifizieren. Der Expressionsunterschied wurde durch ein Southern-Blot Verfahren und semiquantitative PCR verifiziert. Insulin-like Growth Factors gehören zu den vorherrschensten Wachstumsfaktoren des Körpers. Sie sind potente Stimulatoren von Zellüberleben und Wachstum. IGFBP-5, als eines ihrer Bindungs-Proteine ist mit pro-apoptotischer Wirkung in Zusammenhang gebracht worden. Der Expressionsunterschied von IGFBP-5 nach Behandlung mit Paclitaxel lässt die Interpretation zu, dass das Chemotherapeutikum bei Mammakarzinomzellen durch IGFBP-5 einschließende Signalwege zur Apoptose-Induktion führt. Weitere Versuche sollen die Einbindung von IGFBP-5 in die Wirkung anderer, bei der Therapie des Mammakarzinoms etablierter Anti-Tumorsubstanzen untersuchen. Breast cancer is the most common type of cancer in women today. Paclitaxel , a member of the taxanes, is one of the most promising anti-tumor substances in gynaecological oncology. Aim of this work was to find differentially expressed genes in treated and untreated breast- cancer cell lines. This data could give further information on mechanism of chemotherapy and induction of apoptosis, which could lead to new combinations in chemotherapy. Using differential display and subtractive hybridisation to compare genexpression led to identification of the insulin-like growth factor binding protein–5 (IGFBP-5). These results were confirmed by Southern-Blot and semiquantitative PCR. Insulin-like growth factors belong to the most important growth factors of the human cell. They are potent stimulator of cell life and growth. Insulin-like growth factor binding protein is associated with pro-apoptotic activity. The differential expression of IGFBP-5 after treatment with paclitaxel could show that chemotherapy leads to induction of apoptosis using signaling pathways connected with IGFBP-5. Further research should focus on the role of IGFBP-5 in other chemotherapeutic agents.
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- 2008
21. Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition.
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Schroeder C, Gatidis S, Kelemen O, Schütz L, Bonzheim I, Muyas F, Martus P, Admard J, Armeanu-Ebinger S, Gückel B, Küstner T, Garbe C, Flatz L, Pfannenberg C, Ossowski S, and Forschner A
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- Humans, Liquid Biopsy methods, Male, Female, Middle Aged, Aged, Prospective Studies, Adult, Biomarkers, Tumor genetics, Positron Emission Tomography Computed Tomography methods, Aged, 80 and over, Melanoma drug therapy, Melanoma genetics, Melanoma pathology, Immune Checkpoint Inhibitors therapeutic use, Circulating Tumor DNA genetics, Circulating Tumor DNA blood
- Abstract
Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10
-4 . Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p < 0.001). ctDNA was detected in 76.9% of adjuvant patients with relapse (n = 10/13), while all patients without progression (n = 9) remained ctDNA negative. Tumour-informed liquid biopsies are a reliable tool for monitoring treatment response and early relapse in melanoma patients with ICI., (© 2024. The Author(s).)- Published
- 2024
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22. Preoperative Assessment of Medication-Related Osteonecrosis of the Jaw Using [18F]fluoride Positron Emission Tomography (PET)/CT and [18F]fluorodeoxyglucose PET/MRI in Correlation with Histomorphometry and Micro-CT-A Prospective Comparative Study.
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Reinert CP, Pfannenberg C, Gückel B, Dittmann H, la Fougère C, Nikolaou K, Reinert S, Schönhof R, and Hoefert S
- Abstract
Objectives: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings., Methods: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical interventions for seven patients. Bone tracer uptake was classified as high, medium, or low, and surgical samples were evaluated using Micro-CT and histomorphometric analysis., Results: CT showed medullary sclerosis in all patients, and MRI revealed gadolinium enhancement in four patients. PET imaging revealed remarkably elevated [18F]fluoride uptake and moderately increased [18F]FDG uptake in MRONJ compared to healthy jawbones, with both differences being statistically significant. [18F]fluoride uptake was associated with necrosis, bacteria, and inflammatory tissue. Micro-CT data did not show significant differences, but histomorphometric analysis revealed higher osteocyte and lacunae densities in the high [18F]fluoride uptake group, and more necrotic bone in the medium [18F]fluoride uptake group. Bacteria were observed in all areas., Conclusions: In summary, [18F]fluoride PET accurately identified MRONJ extent, revealing functional changes in jawbone remodeling not visible on CT. [18F]FDG PET showed differences in bone and soft tissue, though less pronounced. This method aids in evaluating disease activity and guiding treatment planning, requiring further research for optimal surgical approaches based on tracer uptake.
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- 2024
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23. Image-guided metabolomics and transcriptomics reveal tumour heterogeneity in luminal A and B human breast cancer beyond glucose tracer uptake.
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Yang Q, Deng S, Preibsch H, Schade TC, Koch A, Berezhnoy G, Zizmare L, Fischer A, Gückel B, Staebler A, Hartkopf AD, Pichler BJ, la Fougère C, Hahn M, Bonzheim I, Nikolaou K, and Trautwein C
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- Humans, Female, Fluorodeoxyglucose F18 metabolism, Gene Expression Profiling, Acetates, Serine, Lipids, Breast Neoplasms diagnostic imaging, Breast Neoplasms genetics, Breast Neoplasms metabolism
- Abstract
Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated., Methods: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach., Results: [
18 F]FDG (2-deoxy-2-[fluorine-18]fluoro-d-glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one-carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18 F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade., Conclusion: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18 F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)- Published
- 2024
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24. How [ 18 F]FDG-PET/CT Affects the Management of Patients with Differentiated Thyroid Carcinoma in Clinical Routines.
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Vogel J, Sekler J, Gückel B, Pfannenberg C, Nikolaou K, La Fougère C, Dittmann H, and Reinert CP
- Abstract
Purpose: To investigate the impact of [
18 F]FDG-PET/CT on the management of differentiated thyroid carcinoma (DTC) in routine clinical settings., Material and Methods: In total, 98 patients (55 females, age 56 ± 18 years) with histologically confirmed thyroid cancer, including all types of DTC and poorly differentiated thyroid cancer (PDTC, n = 7), underwent [18 F]FDG-PET/CT for staging or recurrence diagnostics performed using a state-of-the art clinical scanner (Biograph mCT, Siemens Healthineers) with a standardized examination protocol. The impact of PET/CT on clinical decision making was prospectively evaluated using standardized questionnaires completed by the referring physicians before and after PET/CT. Patient outcome was analyzed for OS drawn from patient records., Results: Referring physicians were unable to establish a treatment plan for 81% of patients with thyroid cancer in the absence of PET/CT. The use of PET/CT had a notable influence on patient management, leading to the development of a well-defined treatment plan for 92% of patients. Moreover, after PET/CT a change in pre-PET/CT-intended treatments occurred in 32% of cases, and further invasive diagnostic could be waived in 7% of cases. [18 F]FDG-PET/CT revealed a tumor detection rate of 68% (local tumor: 19%, lymph node metastases: 40%, distant metastases: 42%). HTg levels, when stimulated via TSH, were considerably higher in patients with metastases detected on PET/CT, compared to those without metastatic findings ( p = 0.02). OS was significantly worse in patients with PDTC ( p = 0.002) compared to follicular thyroid cancer (FTC) and PTC or even in patients with distant metastases at first diagnosis ( p = 0.03)., Conclusions: This prospective registry study confirms that [18 F]FDG-PET/CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer by initiating treatments and reducing the uses of additional imaging and invasive tests.- Published
- 2024
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25. Combined Metabolic and Functional Tumor Volumes on [ 18 F]FDG-PET/MRI in Neuroblastoma Using Voxel-Wise Analysis.
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Chaika M, Männlin S, Gassenmaier S, Tsiflikas I, Dittmann H, Flaadt T, Warmann S, Gückel B, and Schäfer JF
- Abstract
Purpose: The purpose of our study was to evaluate the association between the [
18 F]FDG standard uptake value (SUV) and the apparent diffusion coefficient (ADC) in neuroblastoma (NB) by voxel-wise analysis., Methods: From our prospective observational PET/MRI study, a subcohort of patients diagnosed with NB with both baseline imaging and post-chemotherapy imaging was further investigated. After registration and tumor segmentation, metabolic and functional tumor volumes were calculated from the ADC and SUV values using dedicated software allowing for voxel-wise analysis. Under the mean of thresholds, each voxel was assigned to one of three virtual tissue groups: highly vital (v) (low ADC and high SUV), possibly low vital (lv) (high ADC and low SUV), and equivocal (e) with high ADC and high SUV or low ADC and low SUV. Moreover, three clusters were generated from the total tumor volumes using the method of multiple Gaussian distributions. The Pearson's correlation coefficient between the ADC and the SUV was calculated for each group., Results: Out of 43 PET/MRIs in 21 patients with NB, 16 MRIs in 8 patients met the inclusion criteria (PET/MRIs before and after chemotherapy). The proportion of tumor volumes were 26%, 36%, and 38% (v, lv, e) at baseline, 0.03%, 66%, and 34% after treatment in patients with response, and 42%, 25%, and 33% with progressive disease, respectively. In all clusters, the ADC and the SUV correlated negatively. In the cluster that corresponded to highly vital tissue, the ADC and the SUV showed a moderate negative correlation before treatment (R = -0.18; p < 0.0001) and the strongest negative correlation after treatment (R = -0.45; p < 0.0001). Interestingly, only patients with progression ( n = 2) under therapy had a relevant part in this cluster post-treatment., Conclusion: Our results indicate that voxel-wise analysis of the ADC and the SUV is feasible and can quantify the different quality of tissue in neuroblastic tumors. Monitoring ADCs as well as SUV levels can quantify tumor dynamics during therapy.- Published
- 2023
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26. Influence of [ 18 F]FDG-PET/CT on Clinical Management Decisions in Breast Cancer Patients-A PET/CT Registry Study.
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Werner S, Sekler J, Gückel B, la Fougère C, Nikolaou K, Pfannenberg C, Preibsch H, Engler T, and Olthof SC
- Abstract
There is a lack of evidence regarding the clinical impact of [
18 F]fluorodeoxyglucose positron emission tomography/computed tomography ([18 F]FDG-PET/CT, hereinafter referred to as PET/CT), especially regarding management changes and their link to overall survival. We analyzed 52 PET/CTs in 47 stage I-IV breast cancer patients, selected from a prospective oncological PET/CT registry. Indications for PET/CT were primary staging ( n = 15), restaging ( n = 17), and suspected recurrence ( n = 20). PET/CT-induced management changes were categorized as major or minor. PET/CT-induced management changes in 41 of 52 scans (78.8%; 38 of 47 patients (80.9%)), of which major changes were suggested in 18 of 52 scans (34.6%, 17 of 47 patients, 36.2%). PET/CT downstaged 6 of 15 primary staging patients, excluding distant metastases. Major management changes were documented in 3 of 17 restaging exams. PET/CT ruled out clinically suspected recurrence in 6 of 20 cases and confirmed it in 11 of 20. In three cases, locoregional recurrence had already been diagnosed via biopsy. In 30 of 52 exams, additional diagnostic tests were avoided, of which 13 were invasive. PET/CT-based management changes resulted in a 5-year survival rate of 72.3% for the whole study group, 93.3% for the staging group, 53.8% for the restaging group, and 68.4% for the recurrence group. This study shows that PET/CT significantly impacts clinical management decisions in breast cancer patients in different clinical scenarios, potentially determining the patient's tumor stage as the basis for further therapy more reliably and by avoiding unnecessary diagnostic tests.- Published
- 2023
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27. How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World.
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Liang C, Sekler J, Gückel B, Pfannenberg C, Dittmann H, Seith F, Amend B, Nikolaou K, and Reinert CP
- Abstract
Objective: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment., Methods: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics., Results: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases., Conclusion: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases., Key Points: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.
- Published
- 2023
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28. Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism.
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Othman AE, Liang C, Komma Y, Munz M, Kolb M, Rath D, Gückel B, Pohmann R, Nikolaou K, Schwartz M, Küstner T, Martirosian P, and Seith F
- Subjects
- Humans, Female, Middle Aged, Prospective Studies, Respiration, Contrast Media, Spin Labels, Magnetic Resonance Imaging methods, Pulmonary Embolism diagnosis
- Abstract
Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599 © RSNA, 2023.
- Published
- 2023
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29. [18F]Fluoride Positron-Emission Tomography (PET) and [18F]FDG PET for Assessment of Osteomyelitis of the Jaw in Comparison to Computed Tomography (CT) and Magnetic Resonance Imaging (MRI): A Prospective PET/CT and PET/MRI Pilot Study.
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Reinert CP, Pfannenberg C, Dittmann H, Gückel B, la Fougère C, Nikolaou K, and Hoefert S
- Abstract
To investigate imaging features of osteomyelitis of the jaw (OMJ) using [18F]fluoride positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG)-PET compared with computed tomography (CT) and magnetic resonance imaging (MRI) to assess extent and disease activity. Six female patients (55.3 ± 10.0 years) were enrolled for assessment of symptomatic OMJ. 4/6 patients underwent [18F]FDG-PET/MRI and [18F]fluoride-PET/CT, one patient MRI and [18F]fluoride-PET/CT and another patient only [18F]FDG-PET/MRI. Image analysis was performed by two radiologists, an oral and maxillofacial surgeon, and a nuclear medicine specialist. The extent of affected jawbone was analyzed both qualitatively and quantitatively, including the PET tracer uptake, CT-Hounsfield-Units (HU) and MRI parameters in affected and healthy jawbone. All patients had trabecular sclerosis in the affected jawbone compared to healthy jawbone (560 ± 328 HU vs. 282 ± 211 HU; p > 0.05), while 3/6 patients had cortical erosions. Bone marrow edema and gadolinium enhancement were documented in 5/6 patients. In affected jawbone, [18F]fluoride-uptake was increased in all patients compared to healthy jawbone (SUVmean 15.4 ± 4.2 vs. 2.1 ± 0.6; p < 0.05), and [18F]FDG-uptake was moderately higher (SUVmean 1.9 ± 0.7 vs. 0.7 ± 0.2; p > 0.05). The extent of regions with increased metabolic activity was less than the extent of morphologic changes in all patients. Information on jawbone metabolism and inflammation is different from morphologic changes and therefore has the potential to provide a more accurate and objective assessment of the extent and activity of OMJ.
- Published
- 2022
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30. Impact of 18 F-FDG-PET/CT on Clinical Management in Patients with Cholangiocellular Carcinoma.
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Kiefer LS, Sekler J, Gückel B, Kraus MS, la Fougère C, Nikolaou K, Bitzer M, Gatidis S, and Pfannenberg C
- Abstract
Objective: To determine the impact of
18 F-FDG-PET/CT on clinical management of patients with cholangiocellular carcinoma (CCA)., Methods: Patients with CCA undergoing clinically indicated18 F-FDG-PET/CT between 04/2013 and 08/2018 were prospectively included in a local PET/CT registry study. Intended clinical management ("non-treatment" such as watchful-waiting or additional diagnostic tests, and "palliative" or "curative treatment") was recorded before and after PET/CT. Changes in intended management after PET/CT were analyzed., Results: 27 patients (mean age: 60 years, IQR: 51.5-67.5 years, 56% males) with 43 PET/CT examinations were included. Intended management changed in 35/43 cases (81.4%) following PET/CT. Major changes ( i.e., between "non-treatment" and "treatment" strategies or between a "curative" and "palliative" treatment goal) occurred in 27/43 (62.8%) cases. Before PET/CT, additional imaging and/or biopsy were intended in 21/43 (48.8%) and 9/43 (20.9%) cases, respectively. After PET/CT, further imaging was carried out in one case and imaging-targeted biopsy in eight cases. Although the absolute number of biopsies after PET/CT did not decrease, in only one of these eight cases biopsy had already been planned before PET/CT, whereas in the other eight cases, the originally planned biopsies were dispensable after PET/CT., Conclusions:18 F-FDG-PET/CT significantly impacts clinical management of patients with CCA. It guides decisions on treatment strategy (especially curative vs palliative treatment goal) and on additional tests, particularly by helping referring clinicians to avoid unnecessary imaging and by guiding targeted biopsy., Advances in Knowledge: Systematic implementation of18 F-FDG-PET/CT may enable a more appropriate and tailored treatment of patients with CCA, especially in cases of suspected recurrence., (© 2021 The Authors. Published by the British Institute of Radiology.)- Published
- 2021
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31. Is there a link between very early changes of primary and secondary lymphoid organs in 18 F-FDG-PET/MRI and treatment response to checkpoint inhibitor therapy?
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Seith F, Forschner A, Weide B, Gückel B, Schwartz M, Schwenck J, Othman AE, Fenchel M, Garbe C, Nikolaou K, Schwenzer N, la Fougère C, and Pfannenberg C
- Subjects
- Female, Fluorodeoxyglucose F18 pharmacology, Humans, Immune Checkpoint Inhibitors pharmacology, Male, Prospective Studies, Fluorodeoxyglucose F18 therapeutic use, Immune Checkpoint Inhibitors therapeutic use, Positron Emission Tomography Computed Tomography methods
- Abstract
Response assessment or prediction to checkpoint inhibitor therapy (CIT) is an unsolved problem in current routine diagnostics of patients with melanoma. Here, we evaluated very early changes of primary and secondary lymphoid organs under CIT in multiparametric [
18 F]-labeled fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET)/MRI as possible predictors of treatment response and investigated their correlation with baseline blood immune biomarkers. Between October 2014 and November 2017, 17 patients with unresectable melanoma (8 females; 65±11 years) undergoing CIT were prospectively evaluated using whole-body18 F-FDG-PET/MRI before CIT start (t0 ), 2 weeks (t1 ) and 3 months after CIT initiation (t2 ). At each time point, the volume, the18 F-FDG-uptake and the mean apparent diffusion coefficient (ADC) of the spleen as well as the18 F-FDG uptake of the bone marrow were assessed. Relative lymphocyte count (RLC), relative eosinophil count (REC) and neutrophil-lymphocyte ratio (NLR) were assessed at baseline. Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics (iRECIST) and decisions from an interdisciplinary tumor board were used for treatment response evaluation at t2 iRECIST was compared with PET response criteria in solid tumors for image-based response evaluation at different time points. Comparative analysis was conducted with Mann-Whitney U test with false discovery rate correction for multiple testing and correlation coefficients were computed. In lymphoid organs, significant differences (p<0.05) between responders (9/17) and non-responders were found for the18 F-FDG-uptake in the spleen at t1 and the increase of the uptake t1 -t0 (responders/non-responders: standardized uptake value lean body mass 1.19/0.93; +49%/-1%). The best correlation coefficients to baseline biomarkers were found for the18 F-FDG-uptake in the spleen at t1 : NLR, r=-0.46; RLC, r=0.43; REC, r=0.58 (p<0.05), respectively. Compared with the non-responder group, the responder group showed marked increases also in the volume of the spleen (+22%/+10%), the18 F-FDG-uptake of bone marrow (+31%/-9%) at t1 and the ADCmean at t2 (+46%/+15%) compared with t0 , however, not reaching significance. Our findings indicate that an effective systemic immune response in patients undergoing CIT can be detected as a significantly increased spleen activity in18 F-FDG-PET as early as 2 weeks after treatment initiation. TRIAL REGISTRATION NUMBER: NCT03132090, DRKS00013925., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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32. HLA ligandomics identifies histone deacetylase 1 as target for ovarian cancer immunotherapy.
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Peper JK, Bösmüller HC, Schuster H, Gückel B, Hörzer H, Roehle K, Schäfer R, Wagner P, Rammensee HG, Stevanović S, Fend F, and Staebler A
- Abstract
The recent approval of clincially effective immune checkpoint inhibitors illustrates the potential of cancer immunotherapy. A challenging task remains the identification of specific targets guiding immunotherapy. Facilitated by technical advances, the direct identification of physiologically relevant targets is enabled by analyzing the HLA ligandome of cancer cells. Since recent publications demonstrate the immunogenicity of ovarian cancer (OvCa), immunotherapies, including peptide-based cancer vaccines, represent a promising treatment approach. To identify vaccine peptides, we employed a combined strategy of HLA ligandomics in high-grade serous OvCa samples and immunogenicity analysis. Only few proteins were naturally presented as HLA ligands on all samples analyzed, including histone deacetylase (HDAC) 1 and 2. In vitro priming of CD8(+) T cells demonstrated that two HDAC1/2-derived HLA ligands can induce T-cell responses, capable of killing HLA-matched tumor cells. High HDAC1 expression shown by immunohistochemistry in 136 high-grade serous OvCa patients associated with significantly reduced overall survival (OS), whereas patients with high numbers of CD3(+) tumor-infiltrating lymphocytes (TILs) in the tumor epithelium and CD8(+) TILs in the tumor stroma showed improved OS. However, correlating HDAC1 expression with TILs, high levels of TILs abrogated the impact of HDAC1 on OS. This study strengthens the role of HDAC1/2 as an important tumor antigen in OvCa, demonstrating its impact on OS in a large cohort of OvCa patients. We further identified two immunogenic HDAC1-derived peptides, which frequently induce multi-functional T-cell responses in many donors, suitable for future multi-peptide vaccine trials in OvCa patients.
- Published
- 2015
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33. Peptide microarrays for the profiling of cytotoxic T-lymphocyte activity using minimum numbers of cells.
- Author
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Hoff A, Bagû AC, André T, Roth G, Wiesmüller KH, Gückel B, and Brock R
- Subjects
- Cell Count, Cell Line, Tumor, Fluoresceins metabolism, Fluorescent Dyes metabolism, HLA-A Antigens metabolism, HLA-A2 Antigen, Humans, Microarray Analysis, Miniaturization, Mucin-1 immunology, Mucin-1 metabolism, Neoplasms immunology, Neoplasms pathology, Peptide Fragments immunology, Peptide Fragments metabolism, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic pathology, Cytotoxicity Tests, Immunologic, Epitope Mapping methods, Immunotherapy, Adoptive, Neoplasms therapy, T-Lymphocytes, Cytotoxic metabolism
- Abstract
The identification of epitopes that elicit cytotoxic T-lymphocyte activity is a prerequisite for the development of cancer-specific immunotherapies. However, especially the parallel characterization of several epitopes is limited by the availability of T cells. Microarrays have enabled an unprecedented miniaturization and parallelization in biological assays. Here, we developed peptide microarrays for the detection of CTL activity. MHC class I-binding peptide epitopes were pipetted onto polymer-coated glass slides. Target cells, loaded with the cell-impermeant dye calcein, were incubated on these arrays, followed by incubation with antigen-expanded CTLs. Cytotoxic activity was detected by release of calcein and detachment of target cells. With only 200,000 cells per microarray, CTLs could be detected at a frequency of 0.5% corresponding to 1,000 antigen-specific T cells. Target cells and CTLs only settled on peptide spots enabling a clear separation of individual epitopes. Even though no physical boundaries were present between the individual spots, peptide loading only occurred locally and cytolytic activity was confined to the spots carrying the specific epitope. The peptide microarrays provide a robust platform that implements the whole process from antigen presentation to the detection of CTL activity in a miniaturized format. The method surpasses all established methods in the minimum numbers of cells required. With antigen uptake occurring on the microarray, further applications are foreseen in the testing of antigen precursors that require uptake and processing prior to presentation.
- Published
- 2010
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34. Antigen loading of dendritic cells with apoptotic tumor cell-preparations is superior to that using necrotic cells or tumor lysates.
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Inzkirweli N, Gückel B, Sohn C, Wallwiener D, Bastert G, and Lindner M
- Subjects
- Apoptosis, Breast Neoplasms pathology, Cell Line, Tumor, Humans, Lymphocyte Activation, Necrosis, Phagocytosis immunology, T-Lymphocytes immunology, Antigens, Neoplasm immunology, Breast Neoplasms immunology, Dendritic Cells immunology
- Abstract
Background: Loading of dendritic cells (DCs) with tumor cell (TC) preparations is an attractive method for vaccine preparation because the entire antigen repertoire of a tumor is processed and presented by the DCs, thus allowing the simultaneous stimulation of T-helper cells and cytotoxic T-lymphocytes. However, optimal loading conditions have still to be defined., Materials and Methods: DCs were pulsed either with tumor lysates, apoptotic or necrotic preparations of a breast cancer cell line and subsequently used to stimulate autologous T-lymphocytes. Antigen loading was quantified using immunofluorescent-based methods., Results: Four hours co-incubation of apoptotic TCs or tumor lysates with DCs undergoing maturation resulted in effective DC-loading. However, the DCs pulsed with apoptotic TCs were best in stimulating interferon-gamma (INF-gamma) secretion as the effector function of autologous T-cells., Conclusion: Tumor lysates are in common use for DC-based vaccine manufacturing. However, our data indicate an advantage of apoptotic TC-preparations in regard to antigen loading effectiveness as well as the loaded DC's capacity to activate T-cells.
- Published
- 2007
35. A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
- Author
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Gückel B, Stumm S, Rentzsch C, Marmé A, Mannhardt G, and Wallwiener D
- Subjects
- Antigens, Neoplasm metabolism, B7-1 Antigen immunology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Carcinoembryonic Antigen metabolism, Cytokines metabolism, Feasibility Studies, Female, HLA-A2 Antigen, Humans, In Vitro Techniques, Influenza A virus physiology, K562 Cells, Leukocytes, Mononuclear immunology, Melanoma-Specific Antigens, Mucin-1 metabolism, Neoplasm Proteins metabolism, Receptor, ErbB-2 genetics, Receptor, ErbB-2 immunology, T-Lymphocytes metabolism, T-Lymphocytes pathology, Transfection, Vaccination, Viral Matrix Proteins metabolism, B7-1 Antigen metabolism, Breast Neoplasms immunology, HLA-A Antigens immunology, Receptor, ErbB-2 metabolism, T-Lymphocytes immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Adjuvant treatment is still only working in a small percentage of breast cancer patients. Therefore, new strategies need to be developed. Immunotherapies are a very promising approach because they could successfully attack tumor cells in the stage of dormancy. To assess the feasibility of using an allogeneic approach for vaccination of breast cancer patients, we selected a CD80-transfected breast cancer cell line based on its immunogenic properties. Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs). Furthermore, a genetically modified KS variant expressing influenza A matrix protein serving as a surrogate tumor-associated antigen (TAA) was able to stimulate flu peptide-specific T cells alongside the induction of alloresponses in MLTCs. KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3. To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer. Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro. These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer. As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes. In whole cell vaccine trials, monitoring is particularly challenging because of strong alloresponses and limited knowledge of TAAs. In this study, a panel of HER-2/neu epitopes, together with the quantitative real time (qRT)-PCR method to analyze vaccine-induced cytokines secreted by T cells, proved to be highly sensitive and feasible to perform an "immunological staging" following vaccination.
- Published
- 2005
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36. Evaluation of pre-existent immunity in patients with primary breast cancer: molecular and cellular assays to quantify antigen-specific T lymphocytes in peripheral blood mononuclear cells.
- Author
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Rentzsch C, Kayser S, Stumm S, Watermann I, Walter S, Stevanoviç S, Wallwiener D, and Gückel B
- Subjects
- Antigen-Presenting Cells, Antigens, Neoplasm genetics, Carcinoembryonic Antigen genetics, Carcinoembryonic Antigen immunology, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Neoplastic, HLA-A Antigens immunology, HLA-A2 Antigen, Humans, Immunity, Cellular, Interferon-gamma metabolism, Leukocytes, Mononuclear immunology, Membrane Proteins genetics, Membrane Proteins immunology, Mucin-1 genetics, Mucin-1 immunology, Neoplasm Proteins genetics, Neoplasm Proteins immunology, Neoplasm Staging, Peptide Fragments immunology, Receptor, ErbB-2 genetics, Receptor, ErbB-2 immunology, Repressor Proteins genetics, Repressor Proteins immunology, Reverse Transcriptase Polymerase Chain Reaction, Antigens, Neoplasm immunology, Breast Neoplasms immunology, T-Lymphocytes immunology
- Abstract
Purpose: Breast cancers are known to frequently (over)express several well-characterized tumor-associated antigens (TAAs) such as carcinoembryonic antigen, MUC-1, Her-2/neu, and cancer/testis antigens such as NY-ESO-1, SSX-2, and members of the MAGE family. Whereas in melanoma patients, the detection of pre-existing T cell responses to tumor-associated differentiation antigens was a rationale to initiate several vaccination strategies, little is known thus far concerning tumor-specific immunity in breast cancer patients. The objectives of our study were (a) to modify and compare different immunodiagnostic T cell assays with regard to their suitability for clinical applications and (b) to determine endogenous TAA-specific T cell immunity of breast cancer patients at the time point of primary diagnosis., Experimental Design: Using MUC-1- and Her-2/neu-derived HLA-A*0201-restricted peptides as model antigens, we analyzed antigen-dependent IFN-gamma release of T cells by enzyme-linked immunospot (ELISpot) assay, intracellular cytokine flow cytometry (CytoSpot), and quantitative real-time PCR. As an assay independent of T cell function, we performed tetramer staining., Results: In our hands, the quantitative real-time PCR method is most sensitive and a feasible screening test to perform an "immunological staging" of cancer patients. By doing this, we detected in 7 of 13 (54%) of HLA-A*0201(+) breast cancer patients a pre-existent specific cellular immune response to at least one of the investigated TAAs (MUC-1, Her-2/neu, carcinoembryonic antigen, NY-ESO-1, and SSX-2). Four of 21 patients (19%) were found to have a significant Her-2/neu-specific T cell response as defined by a stimulation index >/==" BORDER="0"> 2 (range, 10-88)., Conclusions: Although the clinical relevance of endogenous TAA-specific immunity remains unclear, our findings suggest that patients with primary breast cancer can mount a T cell immune response to their tumor that might be beneficially enhanced by TAA-dependent vaccination strategies in the adjuvant situation.
- Published
- 2003
37. CD40-expressing carcinoma cells induce down-regulation of CD40 ligand (CD154) and impair T-cell functions.
- Author
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Batrla R, Linnebacher M, Rudy W, Stumm S, Wallwiener D, and Gückel B
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Antigen-Presenting Cells immunology, CD40 Antigens biosynthesis, CD40 Ligand biosynthesis, CD40 Ligand genetics, Carcinoma metabolism, Down-Regulation, Humans, Interferon-gamma metabolism, Interleukin-2 metabolism, Lymphocyte Activation immunology, T-Lymphocytes metabolism, T-Lymphocytes, Cytotoxic immunology, Tumor Cells, Cultured, CD40 Antigens immunology, CD40 Ligand immunology, Carcinoma immunology, T-Lymphocytes immunology
- Abstract
The interaction of CD40 expressed by immunocompetent cells with its ligand CD154 on the surface of T-helper cells plays a crucial role in the immune response. Recently, the presence of CD40 was also demonstrated on a variety of carcinomas. Whereas the critical relevance of CD40 in cytotoxic T-cell priming via dendritic cells is already established, the biological role of CD40/CD154 interactions in nonhematopoetic cells is still unclear. In the present study we demonstrate that CD154 expression density is down-regulated on activated T cells on interaction with CD40+ tumor cells. Naive T cells cocultured with CD40+carcinoma showed impaired functionality as indicated by a reduced frequency of IFN-gamma secreting cells, reduced interleukin 2 secretion, impaired proliferation, and a lack of CD154 re-expression on restimulation. In distinction, T-cell effector lysing capacity was not impaired by CD40-expressing tumor cell targets. The present results suggest that in marked contrast to antigen-presenting cells, CD40 expression on carcinoma cells suppresses T-cell activation. Our findings support the statement that CD40 functions are context dependent and imply a new function for CD40 expressed on nonantigen-presenting cells.
- Published
- 2002
38. A MAGE-A1 HLA-A A*0201 epitope identified by mass spectrometry.
- Author
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Pascolo S, Schirle M, Gückel B, Dumrese T, Stumm S, Kayser S, Moris A, Wallwiener D, Rammensee HG, and Stevanovic S
- Subjects
- Amino Acid Sequence, Animals, Antigens, Neoplasm genetics, Breast Neoplasms immunology, Chromatography, High Pressure Liquid, Epitopes, T-Lymphocyte immunology, HeLa Cells, Humans, Mass Spectrometry, Melanoma-Specific Antigens, Mice, Neoplasm Proteins genetics, Peptide Fragments immunology, Peptide Mapping, T-Lymphocytes, Cytotoxic immunology, Transfection, Tumor Cells, Cultured, Antigens, Neoplasm immunology, Epitopes, T-Lymphocyte analysis, HLA-A2 Antigen immunology, Neoplasm Proteins immunology
- Abstract
Peptides presented by HLA-A*0201 molecules on the surface of the human breast carcinoma cell line KS24.22 after IFN-gamma induction were analyzed by the "Predict-Calibrate-Detect" approach, which combines epitope prediction and high-performance liquid chromatography mass spectrometry. One of the predicted epitopes, MAGE-A1(278-286) (KVLEYVIKV), was found to be presented by HLA-A*0201, with an estimated copy number of 18 molecules/cell. HLA-A*0201 transgenic mice (HHD mice) were used to generate CTL lines that stained positive with an HLA-A*0201 tetramer folded around the KVLEYVIKV peptide and killed peptide-loaded mouse target cells expressing HLA-A*0201. IFN-gamma-treated or -nontreated HLA-A*0201 expressing HeLa cells transiently transfected with a plasmid expressing the MAGE-A1 gene stimulated in vitro cytokine production by the CTL lines. Moreover, IFN-gamma-treated KS24.22 cells, but not IFN-gamma-treated HLA-A*0201(+) MAGE-A1(-) cells or IFN-gamma-treated HLA-A*0201(-) MAGE-A1(+) cells, were killed by these CTLS: Thus, the combination of HLA epitope prediction, peptide analysis, and immunological methods is a powerful approach for the identification of tumor-associated epitopes.
- Published
- 2001
39. Interleukin-12 requires initial CD80-mediated T-cell activation to support immune responses toward human breast and ovarian carcinoma.
- Author
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Gückel B, Meyer GC, Rudy W, Batrla R, Meuer SC, Bastert G, Wallwiener D, and Moebius U
- Subjects
- Cell Division drug effects, Dose-Response Relationship, Drug, Female, Genetic Therapy methods, Humans, Immunotherapy methods, Interleukin-7 genetics, Kinetics, Time Factors, Tumor Cells, Cultured, B7-1 Antigen genetics, Breast Neoplasms immunology, Interleukin-12 genetics, Ovarian Neoplasms immunology, T-Lymphocytes immunology
- Abstract
One possible reason for the poor immunogenicity of tumors is the induction of peripheral tolerance by tumor cells that fail to deliver costimulatory signals. Furthermore, T cells stimulated with wild-type tumor cells often fail to secrete cytokines. The present study has been undertaken to identify cytokines that cooperate with CD80 in T-cell activation in vitro toward human breast and ovarian carcinoma cell lines. Tumor cell-mediated T-lymphocyte activation was analyzed directly in allogeneic mixed lymphocyte/tumor cell cultures as proliferation and effector functions were assessed in cytotoxic T-cell assays. Interleukin-7 (IL-7) amplified the proliferative response toward CD80-transfected breast and ovarian carcinomas and stimulated predominantly CD4+ T lymphocytes. IL-12 represses the proliferative response of naive T cells but cooperates with CD80-mediated activation during secondary stimulations. In long-term T-cell cultures, IL-12 synergizes with CD80 expression to stimulate cytolytic CD8+ T-cell lines, which recognize a breast carcinoma line in a human histocompatibility leukocyte antigen-restricted manner. These studies illustrate that costimulation is necessary for tumor cells to function as alloantigen-presenting cells. Furthermore, when added after the priming of T cells with CD80-transfected tumor cells, IL-12 could be helpful in propagating sufficient T-cell numbers to be used in adoptive transfers during cellular immunotherapy.
- Published
- 1999
- Full Text
- View/download PDF
40. Potential of CD80-transfected human breast carcinoma cells to induce peptide-specific T lymphocytes in an allogeneic human histocompatibility leukocyte antigens (HLA)-A2.1+-matched situation.
- Author
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Meyer GC, Batrla R, Rudy W, Meuer SC, Wallwiener D, Gückel B, and Moebius U
- Subjects
- Cell Count, Humans, Immunoenzyme Techniques methods, Interferon-gamma pharmacology, Interleukin-2 pharmacology, Interleukin-4 pharmacology, Time Factors, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha pharmacology, B7-1 Antigen genetics, Breast Neoplasms therapy, HLA Antigens genetics, T-Lymphocytes metabolism
- Abstract
Allogeneic human histocompatibility leukocyte antigen (HLA)-matched tumor cell lines that have been made immunogenic by the transfer of genes encoding for costimulatory molecules such as CD80 are considered to be potential vaccines for the induction of systemic immune reactions in cancer patients. We used a human HLA-A2.1+ CD80-transfected breast carcinoma cell line (KS-CD80) and investigated in vitro the efficiency at which antigen (Ag)-specific responses were induced following the stimulation of allogeneic HLA-A2.1-matched T lymphocytes. The influenza matrix protein M1 was used as a model Ag. It was either endogenously expressed or exogenously loaded as a peptide (matrix protein), and the frequency of the generated specific T cells was determined. The expression of CD80 in KS cells was required for an effective activation and expansion of Ag-specific T cells. This response was augmented following the pretreatment of KS-CD80 cells with interferon-gamma and tumor necrosis factor-alpha. Interleukin-4 (IL-4), IL-7, and IL-12 further increased T-cell expansion. IL-7 was best at supporting the generation of T cells with Ag specificity. This investigation demonstrates that allogeneic CD80+ tumor cells can induce Ag-specific, HLA-restricted T lymphocytes at a high frequency. Our study supports the use of allogeneic cell lines for the induction of specific T-cell responses in tumor patients.
- Published
- 1999
- Full Text
- View/download PDF
41. Without prior stimulation, tumor-associated lymphocytes from malignant effusions lyse autologous tumor cells in the presence of bispecific antibody HEA125xOKT3.
- Author
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Strauss G, Gückel B, Wallwiener D, and Moldenhauer G
- Subjects
- Animals, Ascitic Fluid pathology, Breast Neoplasms pathology, Colonic Neoplasms immunology, Colonic Neoplasms pathology, Female, Humans, Immunophenotyping, Lymphocyte Activation immunology, Mice, Ovarian Neoplasms pathology, Pleural Effusion, Malignant pathology, T-Lymphocyte Subsets immunology, Tumor Cells, Cultured, Antibodies, Bispecific pharmacology, Ascitic Fluid immunology, Breast Neoplasms immunology, Cytotoxicity, Immunologic, Lymphocytes, Tumor-Infiltrating immunology, Ovarian Neoplasms immunology, Pleural Effusion, Malignant immunology
- Abstract
Women suffering from advanced stage ovarian or mammary carcinoma frequently develop malignant ascites or pleural effusions consisting of tumor cells and tumor-associated lymphocytes (TALs). Locoregional immunotherapy with bispecific antibodies (bsAbs), which retarget T cells to tumor cells and induce their lysis, has been applied as an adjuvant treatment in the late stage of the disease. Until now, most of these therapies use peripheral blood mononuclear cells (PBMCs) as effector cells that have been stimulated and expanded ex vivo and loaded with bsAb before reinjection. Here we investigated whether TALs derived from malignant ascites or pleural effusions can be used as bsAb-guided effector cells without prior in vitro stimulation. For this we established a bsAb, HEA125xOKT3, which recognizes the epithelial antigen Egp34 on carcinoma cells and the CD3 molecule on T cells. BsAb HEA125xOKT3 induced lysis of various Egp34-expressing carcinoma lines by stimulated PBMCs. Optimal cytotoxicity was achieved at a bsAb concentration of 1 microg/ml. In three ovarian and two mammary carcinoma patients, we demonstrated efficient lytic activity of lymphocytes, isolated from malignant ascites or pleural effusion. Without prior stimulation, they lysed autologous tumor cells in the presence of bsAb HEA125xOKT3, indicating that they are already activated. Along this line, a subset of CD4+ and CD8+ unstimulated TALs expressed the early activation marker CD69. They are, however, negative for CD95, and only a small subpopulation of CD4+ TALs expresses CD25. OKT3/interleukin 2 stimulation of TALs increased the expression of activation markers on the CD4+ and CD8+ T-cell compartment. The activation markers CD69, CD25, CD95, and DR molecules are up-regulated on both T-cell types. However, lysis of autologous tumor cells by stimulated TALs is not significantly enhanced compared with unstimulated TALs. Our results may offer a novel and promising concept of adjuvant immunotherapy for ovarian and mammary carcinoma patients. Preactivation and expansion of PBMCs can be circumvented by exploring the cytotoxic capacity of unstimulated TALs in the presence of bsAbs in a locoregional therapeutic approach.
- Published
- 1999
42. Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.
- Author
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Lindauer M, Rudy W, Gückel B, Doeberitz MV, Meuer SC, and Moebius U
- Subjects
- CD8-Positive T-Lymphocytes immunology, Cell Division, Gene Expression, Humans, B7-1 Antigen genetics, Colorectal Neoplasms immunology, Gene Transfer Techniques, HLA-DR3 Antigen genetics, Intercellular Adhesion Molecule-1 genetics, Lymphocyte Activation
- Abstract
Colorectal cancer is considered a non-immunogenic malignany. One strategy to augment the immunogenicity of such tumours is represented by the expression of costimulatory molecules by gene transfer. Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells. This demonstrates that the generation of immunogenic tumour cell variants, i.e. for the use as cellular vaccines, requires multiple genetic alterations in the case of non-immunogenic human tumours cells, such as colorectal cancer cells.
- Published
- 1998
- Full Text
- View/download PDF
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