Gastrointest Endosc
September 2024
Division of Gastroenterology and Hepatology, Johns Hopkins Hospital, Department of Medicine, Baltimore, Maryland, USA. Electronic address:
Background And Aims: Patients with sigmoid-type achalasia can be challenging to treat with peroral endoscopic myotomy (POEM). A short myotomy improves technical success; however, outcomes have not previously been evaluated.
Methods: This was a multicenter, international, retrospective study of patients who underwent POEM with short (≤4 cm) or standard esophageal myotomy.
Lancet Haematol
March 2024
Department of Haematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
Background: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL.
Methods: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany.
EBioMedicine
October 2023
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Germany. Electronic address:
Nat Commun
May 2021
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.
The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity.
View Article and Find Full Text PDFJ Immunother Cancer
March 2020
Department of Dermatology, University Hospital Essen, Essen, Germany.
Background: Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.
View Article and Find Full Text PDFOncotarget
August 2019
Department of Urology, Stanford Medical School, Stanford, CA, USA.
Therapy resistance remains a serious dilemma in metastatic castration-resistant prostate cancer (mCRPC) with primary or secondary resistance frequently occurring against any given therapy. Available prognostic models for Abiraterone Acetate (AA) are specifically designed for either pre- or post-chemotherapy settings and mostly based on trial datasets not necessarily reflecting real-life. A score of 0-2 (low-risk) is associated with an OS-probability of 80.
View Article and Find Full Text PDFNat Commun
February 2019
Institute of Neuro- and Sensory Physiology, University Medical Center Göttingen, Humboldtallee 23, 37073, Göttingen, Germany.
Stimulation of the B cell antigen receptor (BCR) triggers signaling pathways that promote the differentiation of B cells into plasma cells. Despite the pivotal function of BCR in B cell activation, the organization of the BCR on the surface of resting and antigen-activated B cells remains unclear. Here we show, using STED super-resolution microscopy, that IgM-containing BCRs exist predominantly as monomers and dimers in the plasma membrane of resting B cells, but form higher oligomeric clusters upon stimulation.
View Article and Find Full Text PDFJ Dtsch Dermatol Ges
February 2019
Department of Dermatology, Mainz University Medical Center, Mainz, Germany.
Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.
View Article and Find Full Text PDFJ Dtsch Dermatol Ges
January 2019
Department of Dermatology, Mainz University Medical Center, Mainz, Germany.
Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.
View Article and Find Full Text PDFJ Immunother Cancer
October 2018
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Background: We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).
Methods: In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded.
Anticancer Res
September 2018
Department of Hematology and Oncology, Augsburg Medical Center, Augsburg, Germany.
Aim: Right- and left-sided primary tumors of colorectal origin differ substantially in several aspects. Recent retrospective analyses show distinct efficacy of EGFR-epidermal growth factor receptor (EGFR)-directed therapies for left- and right-sided primary tumors. Current treatment guidelines have accommodated these findings such that for right-sided primary tumors, EGFR-directed therapy is no longer recommended.
View Article and Find Full Text PDFHaematologica
January 2019
Department of Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine and Medical Center, University of Freiburg, Germany
Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression Fetal hemoglobin levels were measured by high-performance liquid chromatography in patients with higher-risk myelodysplastic syndrome (n=16) and acute myeloid leukemia (n=37) before treatment and after each course of decitabine.
View Article and Find Full Text PDFJCO Precis Oncol
August 2018
University of Freiburg, Freiburg; , , , , , , , , , and , German Cancer Consortium, partner site Freiburg, and German Cancer Research Center, Heidelberg; , Augsburg Medical Center, Augsburg; and , University of Lübeck, Lübeck, Germany.
Purpose: Dramatic advances in our understanding of the molecular pathophysiology of cancer, along with a rapidly expanding portfolio of molecular targeted drugs, have led to a paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report the 2-year experience of the Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one of the first interdisciplinary molecular tumor conferences established in Europe. The role of the MTB is to recommend personalized therapy for patients with cancer beyond standard-of-care treatment.
View Article and Find Full Text PDFRecent Results Cancer Res
November 2018
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases plays an important role in the biology of many cancers. In breast and gastrointestinal cancer, and at lower rates also in additional tumor types, HER2 and its homo- or heterodimerization with HER1 or HER3 are essential for cancer cell growth and survival. Breast cancer patients overexpressing HER2 have a more aggressive course of their disease.
View Article and Find Full Text PDFJ Hematol Oncol
October 2017
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Mantle cell lymphoma (MCL) is characterized by an aggressive clinical course and secondary resistance to currently available therapies in most cases. Therefore, despite recent advances in the treatment of this disease, it is still considered to be incurable in the majority of cases. MCL B cells retain their B cell antigen receptor (BCR) expression during and after neoplastic transformation.
View Article and Find Full Text PDFJ Dtsch Dermatol Ges
October 2017
Department of Dermatology and Allergology, Augsburg Medical Center, Augsburg, Germany.
In addition to dermoscopy, there are other imaging and biophysical methods for the noninvasive diagnosis of skin lesions. Confocal laser microscopy allows for high-resolution imaging of the epidermis and upper dermis. It is particularly suitable in the differential diagnosis of melanocytic lesions.
View Article and Find Full Text PDFAnn Neurol
July 2017
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Objective: Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits.
View Article and Find Full Text PDFHum Gene Ther Methods
June 2017
1 Department of Oncology and Hematology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany .
Adeno-associated virus (AAV) has emerged as a very promising gene therapy vector. To enable tissue-directed gene expression, many artificially generated AAV variants have been established, often isolated from large pools of mutated capsids. Random peptide libraries displayed on AAV capsids have been used successfully to select vectors targeted to a given target cell or tissue in vitro and in vivo.
View Article and Find Full Text PDFHaematologica
September 2016
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Hematology and Oncology, Augsburg Medical Center, Germany
EMBO Mol Med
June 2016
Hubertus Wald Cancer Center, Department of Oncology and Hematology University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Hematology and Oncology, Augsburg Medical Center, Augsburg, Germany
Gene therapy critically relies on vectors that combine high transduction efficiency with a high degree of target specificity and that can be administered through a safe intravenous route. The lack of suitable vectors, especially for gene therapy of brain disorders, represents a major obstacle. Therefore, we applied an in vivo screening system of random ligand libraries displayed on adeno-associated viral capsids to select brain-targeted vectors for the treatment of neurovascular diseases.
View Article and Find Full Text PDFMol Ther
June 2016
Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Cancer Center, Hamburg, Germany; Current address: Department of Hematology and Oncology, Augsburg Medical Center, Augsburg, Germany. Electronic address:
Vectors mediating strong, durable, and tissue-specific transgene expression are mandatory for safe and effective gene therapy. In settings requiring systemic vector administration, the availability of suited vectors is extremely limited. Here, we present a strategy to select vectors with true specificity for a target tissue from random peptide libraries displayed on adeno-associated virus (AAV) by screening the library under circulation conditions in a murine model.
View Article and Find Full Text PDFJ Immunol
November 2015
Department of Oncology and Hematology, Hubertus Wald Tumor Center/University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of Hematology and Oncology, Augsburg Medical Center, 86165 Augsburg, Germany.
PLoS One
May 2016
Department of Hematology and Oncology, Augsburg Medical Center, Interdisciplinary Cancer Center, Augsburg, Germany.
Libraries of randomised peptides displayed on phages or viral particles are essential tools in a wide spectrum of applications. However, there is only limited understanding of a library's fundamental dynamics and the influences of encoding schemes and sizes on their quality. Numeric properties of libraries, such as the expected number of different peptides and the library's coverage, have long been in use as measures of a library's quality.
View Article and Find Full Text PDFGene Ther
October 2015
Department of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf, Martinistr, Hamburg, Germany.
Adeno-associated viral (AAV) vectors yield high potential for clinical gene therapy but, like for other vectors systems, they frequently do not sufficiently transduce the target tissue and their unspecific tropism prevents their application for multifocal diseases such as disseminated cancer. Targeted AAV vectors have been obtained from random AAV display peptide libraries but so far, all vector variants selected from AAV libraries upon systemic administration in vivo retained some collateral tropism, frequently the heart. Here we explored, if this impediment can be overcome by microRNA-regulated transgene cassettes as the combination of library-derived capsid targeting and micro-RNA control has not been evaluated so far.
View Article and Find Full Text PDFThorac Cardiovasc Surg
April 1995
Department of cardiovascular surgery, Augsburg Medical Center, Germany.
Between 1987 and 1994, 39 patients underwent 41 replacements (2 reoperations) of the aortic valve and ascending aorta by composite grafts with mechanical valves. One patient had annuloaortic ectasia, one had a sinus of valsalva aneurysm, 13 patients had a Debakey type I acute dissection, 10 had a Debakey type II acute dissection including two Marfan patients, and 14 had atherosclerotic aneurysms. 6 patients (15%) died within a postoperative period of 30 days.
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