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| 1 | Muscle RING-finger protein-1 (MuRFl) functions and cellular localization are regulated by SUMOl post-translational modification显示文摘The muscle RING-finger protein-1 (MuRFl) is an E3 ubiquitin ligase expressed in skeletal and cardiac muscle tissues and it plays important roles in muscle remodeling. Upregulation of MuRFl gene transcription participates in skeletal muscle atrophy, on contrary downregulation of protein expression leads to cardiac hypertrophy. MuRFl gene point mutations have been found to generate protein aggregate myopathies defined as muscle disorder characterized by protein accumulation in muscle fibers. We have discovered that MuRFl turned out to be also a target for a new post-translational modification arbitrated by conjugation of SUM01 and it is mediated by the SUMO ligases E2 UBC9 and the E3 PIASy/4. SUMOylation takes place at lysine 238 localized at the second coiled-coil protein domain that is required for efficient substrate interaction for polyubiquitination. We provided evidence that SUMOylation is essential for MuRFl nuclear translocation and its mitochondria accumulation is enhanced in hyper? glycemic conditions delivering a stabilization of the overall SUMOylated proteins in cultured myocytes. Thus, our findings add this SUM01 post-translational modification as a new concept to understand muscle disorders related to the defect in MuRFl activity. | Gabriel Heras Arvind Venkat Namuduri Leonardo Traini Ganna Shevchenko Alexander Falk Sara Bergstrom Lind Mi Jia Geng Tian Stefano Gastaldello | 2019 | Journal of Molecular Cell Biology2019，11，5： | 4 |
| 2 | Influence of natural killer cells and perforin-mediated cytolysis on the development of chemically induced lung cancer in A/J mice显示文摘 | Manuela Frese-Schaper Andreas Keil Hideo Yagita Selina Katja Steiner Werner Falk Ralph Alexander Schmid Steffen Frese | 2014 | Cancer Immunology Immunotherapy2014，，6： | 1 |
| 3 | Light and the E3 ubiquitin ligase COP 1/ SPA control the protein stability of the MYB transcription factors PAP 1 and PAP 2 involved in anthocyanin accumulation in Arabidopsis显示文摘 | Alexander Maier Andrea Schrader Leonie Kokkelink Christian Falke Bastian Welter Elisa Iniesto Vicente Rubio Joachim F. Uhrig Martin Hülskamp Ute Hoecker | 2013 | Plant J2013，，4： | 1 |
| 4 | Light and the E3 ubiquitin ligase COP 1/ SPA control the protein stability of the MYB transcription factors PAP 1 and PAP 2 involved in anthocyanin accumulation in Arabidopsis显示文摘 | Alexander Maier Andrea Schrader Leonie Kokkelink Christian Falke Bastian Welter Elisa Iniesto Vicente Rubio Joachim F. Uhrig Martin Hülskamp Ute Hoecker | 2013 | Plant J2013，，4： | 1 |
| 5 | Cell-based vaccines for renal cell carcinoma: genetically-engineered tumor cells and monocyte-derived dendritic cells显示文摘 | Bernhard Frankenberger Sybille Regn Christiane Geiger Elfriede Noessner Christine S. Falk Heike Pohla Miran Javorovic Tobias Silberzahn Susanne Wilde Alexander Buchner Michael Siebels Ralph Oberneder Gerald Willimsky Antonio Pezzutto Thomas Blankenstein D | 2005 | World Journal of Urology2005，，3： | 1 |
| 6 | High rate of complete histopathological response in hepatocellular carcinoma patients after combined transarterial chemoembolization and stereotactic body radiation therapy显示文摘BACKGROUND Liver transplantation(LT)presents a curative treatment option in patients with early stage hepatocellular carcinoma(HCC)who are not eligible for resection or ablation therapy.Due to a risk of up 30%for waitlist drop-out upon tumor progression,bridging therapies are used to halt tumor growth.Transarterial chemoembolization(TACE)and less commonly stereotactic body radiation therapy(SBRT)or a combination of TACE and SBRT,are used as bridging therapies in LT.However,it remains unclear if one of those treatment options is superior.The analysis of explant livers after transplantation provides the unique opportunity to investigate treatment response by histopathology.AIM To analyze histopathological response to a combination of TACE and SBRT in HCC in comparison to TACE or SBRT alone.METHODS In this multicenter retrospective study,27 patients who received liver transplantation for HCC were analyzed.Patients received either TACE or SBRT alone,or a combination of TACE and SBRT as bridging therapy to liver transplantation.Liver explants of all patients who received at least one TACE and/or SBRT were analyzed for the presence of residual vital tumor tissue by histopathology to assess differences in treatment response to bridging therapies.Statistical analysis was performed using Fisher-Freeman-Halton exact test,Kruskal-Wallis and Mann-Whitney-U tests.RESULTS Fourteen patients received TACE only,four patients SBRT only,and nine patients a combination therapy of TACE and SBRT.There were no significant differences between groups regarding age,sex,etiology of underlying liver disease or number and size of tumor lesions.Strikingly,analysis of liver explants revealed that almost all patients in the TACE and SBRT combination group(8/9,89%)showed no residual vital tumor tissue by histopathology,whereas TACE or SBRT alone resulted in significantly lower rates of complete histopathological response(0/14,0%and 1/4,25%,respectively,P value<0.001).CONCLUSION Our data suggests that a combination of TACE and SBRT increases the rate of complete histopathological response compared to TACE or SBRT alone in bridging to liver transplantation. | Ulrike Bauer Sabine Gerum Falk Roeder Stefan Münch Stephanie E Combs Alexander B Philipp Enrico N De Toni Martha M Kirstein Arndt Vogel Carolin Mogler Bernhard Haller Jens Neumann Rickmer F Braren Marcus R Makowski Philipp Paprottka Markus Guba Fabian Geisler Roland M Schmid Andreas Umgelter Ursula Ehmer | 2021 | World Journal of Gastroenterology2021，27，24： | 1 |
| 7 | Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons显示文摘 | Falk A Koch P Kesavan J Takashima Y Ladewig J Alexander M Wiskow O Tailor J Trotter M Pollard S Smith A Brüstle O | | 0，，01： | 1 |
| 8 | Establishing a breast cancer center in Herat,Afghanistan:an implementation study显示文摘Objective:Breast cancer is the most common cancer in women,causing significant mortality in the world,which contributed 11.7%to the overall cancer-related mortality in Afghanistan.In 2018,3062 new breast cancer cases were reported accounting for 29.7%of all cancers in women in the country.However,a comprehensive diagnostic and therapeutic system is lacking in Afghanistan.In this paper,we reported the implementation of a project aiming to establish a comprehensive breast cancer center in Herat province of Afghanistan.Methods:From July 2017,a two-year-program initiated at Kimia Hospital in Herat.This first free diagnostic and therapeutic breast cancer project planned by the Afghanistan Surgeons Society-West and the Verein für Afghanistan-Förderung e.V.,as well supported by three international foundations.The target populations of this project were women presenting with breast problems at Kimia Hospital in Herat and healthcare staff involved in breast cancer diagnosis and management.Results:A group of six medical personnel chosen to represent the breast cancer core team for breast cancer diagnosis and management were trained in India.These caregivers established the breast cancer service and tumor board.During a period of 20 months,a total of 632 women with breast problems presented to Kimia Hospital of whom 44(7.0%)were diagnosed with breast cancer.Diagnosis was established by a physical examination,ultrasonography,mammography,biopsy and histopathology.Treatment included surgery,radiotherapy and chemotherapy.Twelve seminars for 512 healthcare workers,1000 brochures and a movie were prepared for awareness-raising actions.For continuation of this project,potential resource providers were identified.A database was developed to record project findings.Conclusion:Implementation of this comprehensive breast cancer project resulted in significant achievements in healthcare staff capacity building,diagnosis and management of breast cancer patients in Herat province.Data obtained in this project offer Afghan government,public health authorities,and the community the opportunity of improving diagnosis and treatment of breast cancer in Afghanistan. | Aziz-ur-Rahman Niazi Aziz Ahmad Jami Ahmad Zia Shams Ahmad Saeed Mahmoodi Eckart Krapfl Stephan Falk Alexander Buia Ernst Hanisch | 2021 | Global Health Journal2021，5，4： | 0 |
| 9 | Radiotherapy among nonagenarians with anal or rectal carcinoma: should we avoid or adapt treatment?显示文摘Dear editor,Radiotherapy is a cornerstone in the management of anal or rectal cancer. Because elderly patients are often excluded from clinical trials, little is known about radiotherapy’s therapeutic index (efficacy/toxicity ratio) in the geriatric population [1]. Still, the ageing of population imposes the challenge to treat older cancer patients and probably to adjust their treatment [2]. A few studies reported data on radiation-induced toxicities in nonagenarian patients, but data on efficacy are still scarce. For rectal cancer, preoperative radiotherapy programs were suggested to be feasible in elderly patients [3–5], with a preference for short protocols without chemotherapy [4]. For anal cancer, the safety of radiochemotherapy was only reported in limited sets of elderly patients [6]. The objective of the present study was to report efficacy and toxicity data on the radiotherapy treatment of nonagenarian patients with anal or rectal cancer.We analyzed the data of 34 nonagenarian patients with anal or rectal cancers: 27 (79.4%) with a rectal adenocarcinoma and 7 (20.6%) with an anal canal squamous cell carcinoma. | Alexis Vallard Chloé Rancoule Jean-Baptiste Guy Avi Assouline Alexander T. Falk Pierre Auberdiac Julien Langrand-Escure Cyrus Chargari Nicolas Magné | 2017 | Chinese Journal of Cancer2017，36，10： | 0 |
| 10 | Targeting stem cells by radiation: From the biological angle to clinical aspects显示文摘Radiotherapy is a cornerstone of anticancer treatment. However in spite of technical evolutions, important rates of failure and of toxicity are still reported. Although numerous pre-clinical data have been published, we address the subject of radiotherapy-stem cells interaction from the clinical efficacy and toxicity perspective. On one side, cancer stem cells(CSCs) have been recently evidenced in most of solid tumor primary locations and are thought to drive radio-resistance phenomena. It is particularly suggested in glioblastoma, where CSCs were showed to be housed in the subventricular zone(SVZ). In recent retrospective studies, the radiation dose to SVZ was identified as an independent factor significantly influencing overall survival. On the other side, healthy tissue stem cells radio-destruction has been recently suggested to cause two of the most quality of life-impacting side effects of radiotherapy, namely memory disorders after brain radiotherapy, and xerostomia after head and neck radiotherapy. Recent publications studying the impact of a radiation dose decrease on healthy brain and salivary stem cells niches suggested significantly reduced long term toxicities. Stem cells comprehension should be a high priority for radiation oncologists, as this particular cell population seems able to widely modulate the efficacy/toxicity ratio of radiotherapy in real life patients. | Alexis Vallard Sophie Espenel Jean-Baptiste Guy Peng Diao Yaoxiong Xia Anis El Meddeb Hamrouni Majed Ben Mrad Alexander Tuan Falk Claire Rodriguez-Lafrasse Chloé Rancoule Nicolas Magné | 2016 | World Journal of Stem Cells2016，8，8： | 0 |
| 11 | Ion emission from warm dense matter produced by irradiation with a soft x-ray free-electron laser显示文摘We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials. | Josef Krása Tomás Burian Vera Hájková Jaromír Chalupský Šimon Jelínek Katerina Frantálová Michal Krupka Zuzana Kuglerová Sushil Kumar Singh Vojtech Vozda Ludek Vysín MichalŠmíd Pablo Perez-Martin Marion Kühlman Juan Pintor Jakub Cikhardt Matthias Dreimann Dennis Eckermann Felix Rosenthal Sam M.Vinko Alessandro Forte Thomas Gawne Thomas Campbell Shenyuan Ren YuanFeng Shi Trevor Hutchinson Oliver Humphries Thomas Preston Mikako Makita Motoaki Nakatsutsumi Xiayun Pan Alexander Köhler Marion Harmand Sven Toleikis Katerina Falk Libor Juha | 2024 | Matter and Radiation at Extremes2024，9，1： | 0 |
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