المؤلفون: Oliver Riesterer, Adela Ademaj, Emsad Puric, Brigitte Eberle, Marcus Beck, Silvia Gomez, Dietmar Marder, Eva Oberacker, Susanne Rogers, Roger A. Hälg, Thomas Kern, Sonja Schwenne, Jürgen Stein, Emanuel Stutz, Olaf Timm, Sebastian Zschaeck, Mathias S. Weyland, Paraskevi D. Veltsista, Stephen Wyler, Peter Wust, Stephan Scheidegger, Stephan Bodis, Pirus Ghadjar

المصدر: International Journal of Hyperthermia, Vol 39, Iss 1, Pp 1078-1087 (2022)

مصطلحات موضوعية: Bladder cancer, tetramodal therapy, regional hyperthermia, radiochemotherapy, bladder preservation, Medical technology, R855-855.5

الوصف: Background Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT).Methods Patients with stages T2–4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57–58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41–43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design.Results Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3–4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy.Conclusion Tetramodal therapy of T2–T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0265-6736Test; https://doaj.org/toc/1464-5157Test

الوصول الحر: https://doaj.org/article/3124c2542f004dd49d96ffbea0bbc532Test

المؤلفون: Peter Wust, Paraskevi D. Veltsista, Eva Oberacker, Prabhusrinivas Yavvari, Wolfgang Walther, Olof Bengtsson, Anja Sterner-Kock, Marie Weinhart, Florian Heyd, Patricia Grabowski, Sebastian Stintzing, Wolfgang Heinrich, Ulrike Stein, Pirus Ghadjar

المصدر: Cancers, Vol 14, Iss 21, p 5349 (2022)

مصطلحات موضوعية: radiofrequency, amplitude modulation, hyperthermia, colorectal cancer, anticancer effects, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/14/21/5349Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/05fee9da7b5e4a37b3ff560d75fb0265Test

المؤلفون: Alexandros Papalampros, Michail Vailas, Konstantinos Ntostoglou, Maria Lopez Chiloeches, Stratigoula Sakellariou, Niki V. Chouliari, Menelaos G. Samaras, Paraskevi D. Veltsista, Sofia D. P. Theodorou, Aggelos T. Margetis, Anna Bergonzini, Lysandros Karydakis, Natasha Hasemaki, Sophia Havaki, Ioannis I. Moustakas, Antonios Chatzigeorgiou, Timokratis Karamitros, Eleni Patsea, Christos Kittas, Andreas C. Lazaris, Evangelos Felekouras, Vassilis G. Gorgoulis, Teresa Frisan, Ioannis S. Pateras

المصدر: Cancers, Vol 12, Iss 7, p 1825 (2020)

مصطلحات موضوعية: pancreatic ductal adenocarcinoma, spatial heterogeneity, draining lymph nodes, tumor microenvironment, T cell exhaustion, T cell senescence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Methods: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). Results: We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of CD47-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. Conclusion: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/12/7/1825Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/dfc91d009a644ed58f1a7b73b051ec60Test

المؤلفون: Ioannis S. Pateras, Ioannis I Moustakas, Timokratis Karamitros, Teresa Frisan, Sophia Havaki, Sofia D.P. Theodorou, Maria Lopez Chiloeches, Michail Vailas, Evangelos Felekouras, Eleni Patsea, Konstantinos Ntostoglou, Natasha Hasemaki, Anna Bergonzini, Niki V. Chouliari, Stratigoula Sakellariou, Antonios Chatzigeorgiou, Alexandros Papalampros, Christos Kittas, Lysandros Karydakis, Vassilis G. Gorgoulis, Paraskevi D Veltsista, Menelaos G Samaras, Andreas C. Lazaris, Aggelos Margetis

المصدر: Cancers
Volume 12
Issue 7
Cancers, Vol 12, Iss 1825, p 1825 (2020)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, endocrine system diseases, signal regulatory protein alpha (SIRPα), T cell, Cell- och molekylärbiologi, Cell, pancreatic ductal adenocarcinoma, Biology, lcsh:RC254-282, Article, Type 2 immune response, 03 medical and health sciences, 0302 clinical medicine, Immune system, draining lymph nodes, Parenchyma, medicine, tumor microenvironment, CD47, T cell exhaustion, macrophage checkpoint, Tumor microenvironment, spatial heterogeneity, T cell senescence, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Phenotype, digestive system diseases, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Cell and Molecular Biology, neoadjuvant chemotherapy

الوصف: Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Methods: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: a) tumor center (TC), b) invasive front (IF), c) normal parenchyma adjacent to the tumor, and d) tumor positive and negative draining lymph nodes (LNs). Results: We observed: a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs
b) a dominant type 2 immune response in the TME, which is more pronounced in the TC
c) an emerging role of CD47-SIRP&alpha
axis
and d) a similar immune cell topography independently of the neoadjuvant chemotherapy. Conclusion: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9645955b0efe1869e975a2b51c1ced09Test

المؤلفون: Elisa Giovannetti, Paraskevi D. Veltsista, Yehuda G. Assaraf, Marcello Tiseo, Alessandro Leonetti, Btissame El Hassouni

المساهمون: Medical oncology laboratory, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer biology and immunology

المصدر: Drug Resistance Updates, 42, 1-11. Churchill Livingstone
Leonetti, A, Assaraf, Y G, Veltsista, P D, El Hassouni, B, Tiseo, M & Giovannetti, E 2019, ' MicroRNAs as a drug resistance mechanism to targeted therapies in EGFR-mutated NSCLC : Current implications and future directions ', Drug Resistance Updates, vol. 42, pp. 1-11 . https://doi.org/10.1016/j.drup.2018.11.002Test

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Lung Neoplasms, medicine.medical_treatment, Antineoplastic Agents, Drug resistance, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, microRNA, Medicine, Humans, Pharmacology (medical), Epidermal growth factor receptor, Lung cancer, Protein Kinase Inhibitors, Pharmacology, Chemotherapy, biology, business.industry, Mechanism (biology), Kinase, Disease progression, medicine.disease, respiratory tract diseases, ErbB Receptors, MicroRNAs, 030104 developmental biology, Infectious Diseases, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Cancer research, biology.protein, business

الوصف: The introduction of EGFR-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and prognosis of non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. However, these patients display disease progression driven by the onset of acquired mechanisms of drug resistance that limit the efficacy of EGFR-TKI to no longer than one year. Moreover, a small fraction of EGFR-mutated NSCLC patients does not benefit from this targeted treatment due to primary (i.e. intrinsic) mechanisms of resistance that preexist prior to TKI drug treatment. Research efforts are focusing on deciphering the distinct molecular mechanisms underlying drug resistance, which should prompt the development of novel antitumor agents that surmount such chemoresistance modalities. The capability of microRNAs (miRNAs) to regulate the expression of many oncogenic pathways and their central role in lung cancer progression, provided new directions for research on prognostic biomarkers, as well as innovative tools for predicting patients’ response to systemic therapies. Recent evidence suggests that modulation of key miRNAs may also reverse oncogenic signaling pathways, and potentiate the cytotoxic effect of anti-cancer therapies. In this review, we focus on the putative emerging role of miRNAs in modulating drug resistance to EGFR-TKI treatment in EGFR-mutated NSCLC. Moreover, we discuss the current implications of miRNAs analyses in the clinical setting, using both tissue and liquid biopsies, as well as the future potential use of miRNA-based therapies in overcoming resistance to targeted agents like TKIs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e862731498dccd23349e853c3a0c322Test
https://pubmed.ncbi.nlm.nih.gov/30544036Test

المؤلفون: Adela Ademaj, Paraskevi D. Veltsista, Dietmar Marder, Roger A. Hälg, Emsad Puric, Thomas B. Brunner, Hans Crezee, Dorota Gabrys, Martine Franckena, Cihan Gani, Michael R. Horsman, Robert Krempien, Lars H. Lindner, Sergio Maluta, Markus Notter, Griseldis Petzold, Sultan Abdel-Rahman, Antonella Richetti, Andreas R. Thomsen, Pelagia Tsoutsou, Rainer Fietkau, Oliver J. Ott, Pirus Ghadjar, Oliver Riesterer

المساهمون: Radiotherapy, CCA - Cancer Treatment and Quality of Life, CCA - Cancer biology and immunology

المصدر: Strahlentherapie und Onkologie. Urban und Vogel
Strahlentherapie und Onkologie, 199(5), 436-444. Urban und Vogel
Ademaj, A, Veltsista, P D, Marder, D, Hälg, R A, Puric, E, Brunner, T B, Crezee, H, Gabrys, D, Franckena, M, Gani, C, Horsman, M R, Krempien, R, Lindner, L H, Maluta, S, Notter, M, Petzold, G, Abdel-Rahman, S, Richetti, A, Thomsen, A R, Tsoutsou, P, Fietkau, R, Ott, O J, Ghadjar, P & Riesterer, O 2023, ' A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers ', Strahlentherapie und Onkologie, vol. 199, no. 5, pp. 436-444 . https://doi.org/10.1007/s00066-022-01980-9Test
Strahlentherapie und Onkologie

مصطلحات موضوعية: Thermometric parameter, Oncology, Treatment sequence, Radiology, Nuclear Medicine and imaging, Thermal dose, Treatment standardization, Time interval

الوصف: Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. Methods A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. Results The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3–100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter “cumulative equivalent minutes at 43 °C” (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. Conclusion There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e2f84008fbfc0aaf11cd0faa42f6435Test