Article
Cell Biology
Antonio Michelucci, Luigi Sforna, Angela Di Battista, Fabio Franciolini, Luigi Catacuzzeno
Summary: Glioblastoma (GBM) is a deadly brain tumor that invades healthy brain tissue through cell migration and invasion. The precise nature of the K+ channels involved in cell volume regulation in this type of tumor has remained uncertain. This study found that hypotonic-induced cell swelling in GBM U87-MG cells triggers the opening of calcium-activated K+ channels, particularly BKCa and IKCa, which play a key role in the regulatory volume decrease following hypotonic shock.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Leon J. Blankenstein, Nils Cordes, Leoni A. Kunz-Schughart, Anne Vehlow
Summary: In this study, PAK4 was identified as the main regulator of invasion and radio-chemotherapy resistance in glioblastoma cells. By enhancing the number of DNA double-strand breaks and reducing the expression of DNA repair proteins, PAK4 inhibition could improve the radiosensitivity and impair DNA repair in glioblastoma.
Article
Physiology
Beth A. McNally, Amber E. Plante, Andrea L. Meredith
Summary: Daily regulation of BK channel activity in the suprachiasmatic nucleus (SCN) is dependent on the type of Ca2+ channels, with LTCCs playing a major role during the day and less so at night. SCN neurons lack a specific subtype of Ca2+ channels responsible for BK current activation, suggesting a complex interplay between different LTCC subtypes.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Po-Ming Wu, Pei-Chun Lai, Hsin-Yen Cho, Tzu-Hsien Chuang, Sheng-Nan Wu, Yi-Fang Tu
Summary: Phenobarbital is an anticonvulsant and a hypnotic that acts on the GABA(A) receptors in the central nervous system to facilitate synaptic inhibition. It has been found to inhibit various ionic currents, independent of GABA(A) receptors, and this inhibition is not counteracted by GABA antagonists or chloride channel blockers.
Article
Pharmacology & Pharmacy
Shuai Guo, Zhenhui Chen, Peng-Sheng Chen, Michael Rubart
Summary: Ondansetron inhibits hSK2 currents even under altered ionic conditions, potentially showing antiarrhythmic effects.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Atikan Wubulikasimu, Ziyan He, Yanping Long, Fuchu Yuan, Wenqian Hou, Qiong Liao, Haiyan Chen, Mingqiang Rong
Summary: This study aimed to enhance the potency of IK channel activating peptides derived from HNTX-I and elucidate the molecular mechanism underlying the interaction between HNTX-I and the IK channel. By employing virtual alanine scanning mutagenesis, key residues crucial for the HNTX-I and IK channel interaction were identified. Molecular docking was used to clarify the binding interface between HNTX-I and the IK channel. The study provides valuable insights into the development of activators with enhanced potency and selectivity for the IK channel.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Physiology
Concetta Caglioti, Federico Palazzetti, Lorenzo Monarca, Raffaele Lobello, Maria Rachele Ceccarini, Rossana Giulietta Iannitti, Roberta Russo, Francesco Ragonese, Chiara Pennetta, Antonella De Luca, Michela Codini, Bernard Fioretti
Summary: Glioblastomas (GBs) are highly malignant and invasive tumors in the central nervous system. Phosphatidylinositol 3-kinase (PI3K) activity and intermediate conductance calcium-activated potassium (KCa3.1) current play important roles in GB biology. This study found that KCa3.1 channel activity can be modulated by PI3KC2 beta, leading to a reduction in intracellular calcium concentration and open probability. The findings have therapeutic implications for preventing chemo- and radioresistance mechanisms in GB.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Taro Koya, Masaya Watanabe, Hiroyuki Natsui, Takahide Kadosaka, Takuya Koizumi, Motoki Nakao, Hikaru Hagiwara, Rui Kamada, Taro Temma, Toshihisa Anzai
Summary: This study found that inhibiting nNOS can increase the inducibility of atrial arrhythmia, and a specific SK channel blocker called apamin can reverse the increased inducibility of arrhythmia. Apamin can mitigate the abbreviation of APD without altering Ca2+ transient, suggesting an underlying mechanism of posttranslational modification of SK channels.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ning-Ping Foo, Yu-Fan Liu, Ping-Ching Wu, Chung-Hsi Hsing, Bu-Miin Huang, Edmund-Cheung So
Summary: This study found that MDZ suppressed the current density of I-K(DR) in a concentration-, time-, and state-dependent manner in Jurkat T-lymphocytes, and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Meryem H. H. Cetin, Thorsten Rieckmann, Konstantin Hoffer, Britta Riepen, Sabrina Christiansen, Fruzsina Gatzemeier, Simon Feyerabend, Melanie Schoof, Ulrich Schueller, Cordula Petersen, Martin Mynarek, Kai Rothkamm, Malte Kriegs, Nina Struve
Summary: In this study, the researchers found that high expression of Wee1 kinase is associated with poor prognosis in glioblastoma. They demonstrated that inhibition of Wee1 can sensitize glioblastoma cells to radiotherapy, regardless of the expression of EGFRvIII.
RADIATION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maurish Bukhari, Han Deng, Darren Sipes, Marisa Ruane-Foster, Kayla Purdy, Craig D. Woodworth, Shantanu Sur, Damien S. K. Samways
Summary: This study reveals that elevated cytosolic Ca2+ levels stimulate rapid uptake and nuclear accumulation of a DNA-binding fluorescent dye in cervical cancer cells, dependent on activation of intermediate conductance Ca2+-activated K+ channels. Comparisons between cancerous and healthy cervical epithelial cells show significant differences in functional K+ channel activity, which correlates with the incidence of dye uptake. Activation of these channels sensitizes cancer cells to growth suppressant effects, suggesting potential use of channel activators to enhance penetration of toxins into cancer cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Peripheral Vascular Disease
Yuan Sun, Cuicui Wang, Na Zhang, Fang Liu
Summary: Melatonin supplementation ameliorates hypertension in pregnant mice with gestational hypertension and enhances uterine artery endothelial response to acetylcholine. The BKCa potassium channel is involved in this effect of melatonin on uterine artery endothelial function, promoting its expression and function. Ultimately, melatonin improves pregnancy outcomes in pregnant mice.
HYPERTENSION RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Tianyu Wang, Hui Wang, Fan Yang, Kuan Gao, Shuya Luo, Lichuan Bai, Ke Ma, Mei Liu, Shuwei Wu, Huijie Wang, Zaixing Chen, Qinghuan Xiao
Summary: This study revealed a new anticancer mechanism of honokiol by inhibiting cell proliferation through targeting Ano1 Ca2+-activated Cl- channels. Honokiol more potently inhibited Ano1 currents compared to Ano2 currents, with three critical amino acids (R429, K430, and N435) identified for honokiol-induced Ano1 inhibition.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Ji Yeon Lee, Haifeng Zheng, Kenton M. Sanders, Sang Don Koh
Summary: In murine antral smooth muscle cells, low-voltage-activated inward currents are generated by K+ influx via KA channels, rather than T-type Ca2+ channels, Ca2+-activated Cl- channels, or nonselective cation channels.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Federico Brandalise, Martino Ramieri, Emanuela Pastorelli, Erica Cecilia Priori, Daniela Ratto, Maria Teresa Venuti, Elisa Roda, Francesca Talpo, Paola Rossi
Summary: Glioblastoma is the most malignant primary brain tumor characterized by invasive cancer cells infiltrating the brain and interacting with non-neuronal cell types. In this study, it is shown that the sodium-calcium exchanger (NCX) is highly expressed and functionally active in the lamellipodia compartment of GBM cells during migration. NCX blockade impairs lamellipodia formation and maintenance, as well as GBM cell migration. These findings suggest that NCX in the lamellipodia may serve as a potential target for treating brain tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Volker Arndt, Daniela Doege, Stefan Froehling, Peter Albers, Hana Alguel, Ralf Bargou, Carsten Bokemeyer, Martin Bornhaeuser, Christian H. Brandts, Peter Brossart, Sara Yvonne Brucker, Tim H. Bruemmendorf, Hartmut Doehner, Norbert Gattermann, Michael Hallek, Volker Heinemann, Ulrich Keilholz, Thomas Kindler, Cornelia von Levetzow, Florian Lordick, Ulf Peter Neumann, Christoph Peters, Dirk Schadendorf, Stephan Stilgenbauer, Thomas Zander, Daniel Zips, Delia Braun, Thomas Seufferlein, Gerd Nettekoven, Michael Baumann
Summary: The capacities of German Comprehensive Cancer Centers (CCCs) in various aspects of oncology care were significantly affected during the first 2 years of the COVID-19 pandemic. Follow-up, psycho-oncologic care, and tumor surgery were particularly impacted, along with other areas of multidisciplinary oncological care. This study highlights the importance of developing strategies to prevent similar limitations in the future.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Laura Uder, Marcel Nachbar, Sarah Butzer, Jessica Boldt, Sabrina Baumeister, Michael Bitzer, Alfred Koenigsrainer, Thomas Seufferlein, Ruediger Hoffmann, Sergios Gatidis, Konstantin Nikolaou, Daniel Zips, Daniela Thorwarth, Cihan Gani, Simon Boeke
Summary: This study reported on the use of online magnetic resonance guided radiotherapy for liver metastases. The results showed high local control rates and improvements in patient reported outcome measures and quality of life. Further prospective trials are ongoing to define the patient population that will benefit most from this online adaptive workflow.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Monica Lo Russo, Marcel Nachbar, Aisling Barry, Shree Bhide, Amy Chang, William Hall, Martijn Intven, Corrie Marijnen, Femke Peters, Bruce Minsky, Paul B. Romesser, Reith Sarkar, Alex Tan, Simon Boeke, Daniel Wegener, Sarah Butzer, Jessica Boldt, Sergios Gatidis, Konstantin Nikolaou, Daniela Thorwarth, Daniel Zips, Cihan Gani
Summary: This study investigated the impact of rectal ultrasound gel filling on interobserver variability in the delineation of primary rectal tumor volumes. The study found that rectal ultrasound gel filling can improve interobserver agreement and may be a useful tool for future dose escalation strategies.
CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
(2023)
Article
Oncology
Siyer Roohani, Juergen Loskutov, Jens Heufelder, Felix Ehret, Lena Wedeken, Manuela Regenbrecht, Rica Sauer, Daniel Zips, Andrea Denker, Antonia M. Joussen, Christian R. A. Regenbrecht, David Kaul
Summary: A pilot study was conducted using patient-derived 3D cell cultures to investigate the effects of photon and proton radiation on different subtypes of localized high-grade soft tissue sarcoma (STS). The study found pronounced differences in radiosensitivity among different subtypes of STS, and showed that photon and proton radiation had similar dose-dependent cell-killing effectiveness in the 3D cell cultures.
Article
Oncology
Rolf D. Issels, Stefan Boeck, Uwe Pelzer, Ulrich Mansmann, Pirus Ghadjar, Lars H. Lindner, Markus Albertsmeier, Martin K. Angele, Michael Schmidt, Yujun Xu, Marcus Bahra, Johann Pratschke, Michael Schoenberg, Wolfgang E. Thasler, Christoph Salat, Oliver J. Stoetzer, Wolfram T. Knoefel, Dirk Graf, Rudiger Wessalowski, Verena Keitel-Anselmino, Alfred Koenigsrainer, Michael Bitzer, Daniel Zips, Michael Bamberg, Rainer Fietkau, Oliver Ott, Maciej Kawecki, Lucian Wyrwicz, Piotr Rutkowski, Markus Rentsch, Juliana Ababei, Peter Reichardt, Marco Rigamonti, Bernhard Weber, Sultan Abdel-Rahman, Katharina Tschoep-Lechner, Karl-Walter Jauch, Christiane J. Bruns, Helmut Oettle, Michael von Bergwelt-Baildon, Volker Heinemann, Jens Werner
Summary: In this randomized controlled trial, the addition of cisplatin to gemcitabine with regional hyperthermia did not significantly improve disease-free survival in resected pancreatic ductal adenocarcinoma, but it showed a difference in post-recurrence survival and a trend for improved overall survival.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Sebastian Regnery, Chiara de Colle, Chukwuka Eze, Stefanie Corradini, Christian Thieke, Oliver Sedlaczek, Heinz-Peter Schlemmer, Julien Dinkel, Ferdinand Seith, Annette Kopp-Schneider, Clarissa Gillmann, C. Katharina Renkamp, Guillaume Landry, Daniela Thorwarth, Daniel Zips, Claus Belka, Oliver Jaekel, Juergen Debus, Juliane Hoerner-Rieber
Summary: This study aims to explore the clinical feasibility of MR-guided online adaptive radiotherapy for locally-advanced non-small-cell lung cancer (LA-NSCLC). The study will be conducted at three German university hospitals, with 30 patients receiving MR-guided online adaptive radiotherapy along with chemotherapy. The primary endpoints are successful completion of online adapted fractions and on-table time.
RADIATION ONCOLOGY
(2023)
Article
Oncology
Felix Mehrhof, Paula Bergengruen, Jin-Hong Gerds-Li, Andrea Jahn, Anne Kathrin Kluge, Abdul Parwani, Daniel Zips, Leif-Hendrik Boldt, Felix Schoenrath
Summary: This study discussed the experience of two patients with incessant ventricular tachycardia (VT) under long-term left ventricular assist device (LVAD) therapy. Cardiac radioablation (cRA) with a single dose of 25 Gy was used as a last resort treatment option. Although rhythm conversion failed in both patients, one patient was stabilized and discharged before succumbing to a fatal bleeding complication, while the other patient required additional ablation and died 50 days later. Strategies for post-procedural generation of stabilized rhythm should be established for these patients.
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)
Article
Oncology
Paula Maria Bergengruen, Pablo Hernaiz Driever, Volker Budach, Daniel Zips, Arne Gruen
Summary: This case report presents a 6-year-old boy with DIPG who received a second course of re-irradiation as part of an individual multimodal approach. The second course of re-irradiation was well tolerated and resulted in a survival of 24 months after initial diagnosis.
STRAHLENTHERAPIE UND ONKOLOGIE
(2023)
Article
Oncology
Gueliz Acker, Marcel Nachbar, Nina Soffried, Bohdan Bodnar, Anastasia Janas, Kiril Krantchev, Goda Kalinauskaite, Anne Kluge, David Shultz, Alfredo Conti, David Kaul, Daniel Zips, Peter Vajkoczy, Carolin Senger
Summary: Neoadjuvant stereotactic radiosurgery (NaSRS) is becoming increasingly important in the treatment of brain metastases. Our analysis showed that there was no significant difference in tumor volume pre- and postoperatively, and smaller tumors had a higher risk of volume increase. However, contouring resection cavities remains a challenge.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
C. De-Colle, A. Kirby, N. Russell, S. F. Shaitelman, A. Currey, E. Donovan, E. Hahn, K. Hang, C. N. Anandadas, F. Mahmood, E. L. Lorenzen, D. van den Bongard, M. L. Groot Koerkamp, A. C. Houweling, M. Nachbar, D. Thorwarth, D. Zips
Summary: Research in the field of local and locoregional breast cancer radiotherapy aims to optimize treatment outcomes and minimize treatment-related toxicities. Adaptive radiotherapy (ART) takes into account anatomical variations in the target area and organs at risk (OARs) during treatment, resulting in re-optimized treatment plans. This review examines the use of MR-guided and CT-guided ART in different clinical scenarios for breast cancer patients and discusses their advantages and challenges.
CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
(2023)
Article
Oncology
Siyer Roohani, Felix Ehret, Marta Kobus, Anne Floercken, Sven Maerdian, Daniel Rau, Silvan Wittenberg, Armin Jarosch, Robert Oellinger, Daniel Zips, David Kaul
Summary: The study examines the pattern of local recurrence in patients with high-grade soft tissue sarcomas who received pre-or postoperative radiotherapy. The majority of recurrences were found within the planned target volume, indicating that inadequate target volume definition may not be the primary cause of recurrence. Importance rating: 8/10.
ADVANCES IN RADIATION ONCOLOGY
(2023)
Article
Oncology
Luisa Allwohn, Josy Wolfgang, Julia Onken, David Wasilewski, Siyer Roohani, Daniel Zips, Felix Ehret, David Kaul
Summary: This study analyzes the influence of various tumor and patient characteristics on survival outcomes in patients with oligodendrogliomas (ODG) who have the 1p/19q-codeletion and IDH mutation. The results show that extent of resection, radiotherapy, and chemotherapy are associated with improved progression-free survival (PFS) in WHO grade 2 ODG, while only radiochemotherapy contributes to decreased risk of progression in WHO grade 3 ODG.
CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
(2023)
Article
Oncology
Haidara Almansour, Fritz Schick, Marcel Nachbar, Saif Afat, Victor Fritz, Daniela Thorwarth, Daniel Zips, Felix Bertram, Arndt-Christian Mueller, Konstantin Nikolaou, Ahmed E. Othman, Daniel Wegener
Summary: This study investigated the dynamics of lesion ADC in patients with prostate cancer undergoing MR-guided radiation therapy on a 1.5T MR-Linac. The results showed a significant increase in lesion ADC during radiotherapy, suggesting that lesion ADC can be used as a biomarker for evaluating treatment response. However, the absolute ADC values calculated by the algorithm of the MR-Linac manufacturer showed systematic deviations from values obtained on a diagnostic 3T MRI system.
RADIOLOGY AND ONCOLOGY
(2023)
Article
Oncology
Mirjam Renovanz, Sylvia C. Kurz, Johannes Rieger, Bianca Walter, Hannes Becker, Hanni Hille, Paula Bombach, David Rieger, Lucia Grosse, Lara Haeusser, Marco Skardelly, Daniel J. Merk, Frank Paulsen, Elgin Hoffmann, Cihan Gani, Manuela Neumann, Rudi Beschorner, Olaf Riess, Cristiana Roggia, Christopher Schroeder, Stephan Ossowski, Sorin Armeanu-Ebinger, Axel Gschwind, Saskia Biskup, Martin Schulze, Falko Fend, Stephan Singer, Lars Zender, Claudia Lengerke, Sara Yvonne Brucker, Tobias Engler, Andrea Forschner, Arnulf Stenzl, Oliver Kohlbacher, Sven Nahnsen, Gisela Gabernet, Sven Fillinger, Benjamin Bender, Ulrike Ernemann, Oeznur Oener, Janina Beha, Holly Sundberg Malek, Yvonne Moeller, Kristina Ruhm, Marcos Tatagiba, Jens Schittenhelm, Michael Bitzer, Nisar Malek, Daniel Zips, Ghazaleh Tabatabai
Summary: This study investigates the feasibility and clinical utility of molecular profiling and targeted therapy in patients with advanced tumors in the nervous system. The results show that 93.1% of patients can receive biomarker-guided therapy recommendations, with treatment initiated in 22.6% of cases and a progression-free survival ratio >1.3 observed in 31.3% of patients. These findings support the clinical efficacy of biomarker-guided therapies in neuro-oncology patients and have implications for future clinical trials and care.
NEURO-ONCOLOGY ADVANCES
(2023)
Article
Oncology
Steffen Loeck, Annett Linge, Fabian Lohaus, Nadja Ebert, Volker Gudziol, Alexander Nowak, Ingeborg Tinhofer, Goda Kalinauskaite, Maja Guberina, Martin Stuschke, Panagiotis Balermpas, Jens von der Gruen, Anca-Ligia Grosu, Juergen Debus, Ute Ganswindt, Claus Belka, Jan C. Peeken, Stephanie E. Combs, Chiara De-Colle, Daniel Zips, Gustavo B. Baretton, Mechthild Krause, Michael Baumann
Summary: Prognostic biomarker signatures were developed for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary radiochemotherapy. The study identified several clinical parameters and biomarkers associated with loco-regional tumor control and overall survival. Multiple biomarker signatures were defined and showed significant patient stratifications for the endpoints. Further validation is needed before potential application in an interventional trial.
RADIOTHERAPY AND ONCOLOGY
(2022)