Only EBUS-Guided Mediastinal Lymph Node Cryobiopsy Enabled Immunotherapy in a Patient with Non-Small Cell Lung Cancer.

Personalized treatment of metastatic non-squamous non-small cell lung cancer (NSCLC) requires detailed molecular characterization of the tumour including detection of predictive driver mutations and programmed death ligand 1 (PD-L1) expression. Complete detection is influenced by the amount of tumour cells sampled as well as their quality. Different sampling techniques may be necessary to provide sufficient tumour material for comprehensive molecular characterization.

Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial.

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis.

Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis.

Background: Identification of variable epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC) is important for the selection of appropriate targeted therapies. This meta-analysis was conducted to provide a worldwide overview of EGFR mutation and submutation (specifically exon 19 deletions, exon 21 L858R substitutions, and others) prevalence, and identify important covariates that influence EGFR mutation status in patients with advanced NSCLC to address this clinical data gap.

Methods: Embase and MEDLINE in Ovid were searched for studies published between 2004 and 2019 with cohorts of ≥ 50 adults with EGFR mutations, focusing on stage III/IV NSCLC (≤ 20% of patients with stage I/II NSCLC).

Influence of Pharyngeal Anaesthesia on Post-Bronchoscopic Coughing: A Prospective, Single Blinded, Multicentre Trial.

Background: Local anaesthesia of the pharynx (LAP) was introduced in the era of rigid bronchoscopy (which was initially a conscious procedure under local anaesthetic), and continued into the era of flexible bronchoscopy (FB) in order to facilitate introduction of the FB. LAP reduces cough and gagging reflex, but its post-procedural effect is unclear. This prospective multicentre trial evaluated the effect of LAP on coughing intensity/time and patient comfort after FB, and the feasibility of FB under propofol sedation alone, without LAP.

Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis.

Objectives: The purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis.

Background: Late gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques.

Transbronchial cryobiopsy increases diagnostic confidence in interstitial lung disease: a prospective multicentre trial.

Introduction: The accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy.

Life-threatening pneumonitis after first-line treatment with osimertinib for primary T790M mutated non-small cell lung cancer.

Epithelial growth factor receptor (EGFR) directed tyrosine kinase inhibitor (TKI) treatment is the standard approach in patients with advanced, EGFR-mutated non-small cell lung cancer (NSCLC). Although benefit/risk ratio is favorable for these TKI and side effects are manageable in the vast majority of patients, severe and even life-threatening side effects have been reported. TKI-induced interstitial lung disease (ILD) has been reported for single cases in modest severity, predominantly in EGFR-TKI pretreated patients.

A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies.

Background: Bloodstream infections (BSIs) caused by enterobacteria remain a leading cause of mortality in patients with chemotherapy-induced neutropenia. The rate and type of colonization and infection with ESBL-producing Enterobacteriaceae (ESBL-E) and their mode of transmission in German cancer centres is largely unknown.

Methods: We performed a prospective, observational study at five German university-based haematology departments.

[Endocrine abnormalities in a young patient with metastatic cancer - case 3/2013].

History And Admission Findings: We report on a 24-year-old male patient who presented with worsening of the general condition and abdominal pain.

Investigations: On physical examination, gynecomastia was noted. Laboratory tests showed manifest hyperthyroidism.

[Unusual cause of macrohematuria in a 29-year-old woman].

History And Admission Findings: We report on the case of a young women presenting with macrohaematuria, petechiae and strong headaches.

Investigations: Laboratory showed a thrombotic microangiopathy with helmet cells, increased LDH levels (>600 U/l), and thrombocytopenia (<40,000/μl).

Diagnosis, Treatment And Course: Due to strong haemolytic activity and headache with blurred vision, immediate plasma separation with fresh frozen plasma was commenced.

Integrated FDG-PET/CT for detection, therapy monitoring and follow-up of granulocytic sarcoma. Initial results.

Aim: Granulocytic sarcomas (GS) are rare extramedullary manifestations of myeloid or lymphoblastic leukaemia. Laboratory examinations are of limited use for diagnosis of extramedullary disease. Radiological imaging based on morphology is challenging.

Matrilysin (MMP-7) is a novel broadly expressed tumor antigen recognized by antigen-specific T cells.

Purpose: A prerequisite for the development of vaccination strategies is the identification and characterization of relevant tumor-associated antigen. Using microarray and reverse transcription-PCR analysis, we found matrix metalloproteinase (MMP)-7 to be extensively up-regulated in renal cell carcinomas and expressed in a broad variety of malignant cells. MMP-7 can promote cancer invasion and angiogenesis by proteolytic cleavage of extracellular matrix and basement membrane proteins, thus making it a promising target in the context of immunotherapies.

Generation of antigen-specific CTL responses using RGS1 mRNA transfected dendritic cells.

Advances in tumor immunology and Identification of tumor-associated antigens (TAAs) provide a basis for the development of novel immunotherapies to treat malignant diseases. In order to identify novel TAAs, we performed comparative microarray analysis of (heterogeneous) tissues and found regulator of G protein-signaling 1 (RGS1) extensively up-regulated in renal cell carcinoma (RCC) tissues. To examine the possible function of this molecule as a novel, broadly applicable TAA, synthetic full-length RGS1-mRNA was synthesized for the transfection of monocyte-derived dendritic cells (DCs).

Identification and characterization of T-cell epitopes deduced from RGS5, a novel broadly expressed tumor antigen.

Purpose: Identification of tumor-associated antigens and advances in tumor immunology resulted in the development of vaccination strategies to treat patients with malignant diseases. In a novel experimental approach that combined comparative mRNA expression analysis of defined cell types with the characterization of MHC ligands by mass spectrometry, we found that regulator of G protein signaling 5 (RGS5) is extensively up-regulated in a broad variety of malignant cells, and we identified two HLA-A2- and HLA-A3-binding peptides derived from the RGS5 protein. Interestingly, RGS5 was recently shown to be involved in tumor angiogenesis.

Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients.

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell-based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.

Dose-dependent biphasic induction and transcriptional activity of nuclear factor kappa B (NF-kappaB) in EA.hy.926 endothelial cells after low-dose X-irradiation.

Purpose: Low-dose radiotherapy is known to exert an anti-inflammatory effect, but the underlying radiobiological mechanisms are still elusive. It was recently reported that transforming growth factor (TGF) beta1 essentially contributes to the reduced adhesion of peripheral blood mononuclear cells to endothelial cells at low-dose X-irradiation. As the transcription factor nuclear factor kappa B (NF-kappaB) is crucially involved in mediating an inflammatory response by inducing the expression of cytokines and adhesion molecules, NF-kappaB DNA binding and transcriptional activity as well as its impact on the expression of TGF-beta1 in EA.

Generating data for databases--the peptide repertoire of HLA molecules.

During the past few years, a huge amount of information about HLA-presented peptides has been compiled: several thousand naturally processed ligands of such cell surface receptors are already known. Nevertheless, our knowledge covers only a minute proportion of the total peptide repertoire. The overall amount of different peptides presented by one given HLA class I molecule lies between 1000 and 10000 individual sequences per cell.

Heat shock protein 70 membrane expression and melanoma-associated marker phenotype in primary and metastatic melanoma.

Cell membrane localization of the 72 kDa heat shock protein 70 (Hsp70) has been found on different tumour cell lines, on biopsy material from solid tumours and metastases and on leukaemic blasts from acute myelogenous leukaemia patients, but not on the corresponding normal tissues, as determined by flow cytometry using the Hsp70-specific monoclonal antibody C92F3B1. In the present study Hsp70 membrane expression was studied on primary malignant melanomas, melanoma metastases, melanocytes, human skin fibroblasts and peripheral blood lymphocytes, together with expression of the melanoma-associated markers Mel-1, Mel-2 and Mel-5, major histocompatibility complex class I and the fibroblast-specific marker ASO2. As previously shown, fibroblasts and peripheral blood lymphocytes from healthy human volunteers were found to be negative for Hsp70 and for the melanoma-associated markers Mel-1, Mel-2 and Mel-5.

A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity.

Compared with normal cells, tumor cell lines exhibit an unusual plasma membrane localization of heat shock protein 70 (Hsp70). This tumor-selective Hsp70 membrane expression has been found to correlate with an increased sensitivity to lysis mediated by human natural killer (NK) cells that transiently adhere to plastic following cytokine stimulation. A human Hsp70-specific monoclonal antibody (mAb) detects membrane-bound Hsp70 on viable tumor cells and blocks the immune response of NK cells against Hsp70-expressing tumor cells.

Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients.

A tumor-selective cell surface localization of heat shock protein 70 (Hsp70), the major heat-inducible member of the Hsp70 group, correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells and, therefore, might be of clinical relevance. With the exception of mammary carcinomas, an Hsp70 plasma membrane expression was found on freshly isolated human biopsy material of colorectal, lung, neuronal, and pancreas carcinomas, liver metastases, and leukemic blasts of patients with acute myelogenous leukemia. Since normal tissues and bone marrow of healthy human individuals do not express Hsp70 on the cell surface, Hsp70 can be considered as a tumor-selective structure in vivo.

Population genetics of nine short tandem repeat (STR) loci - DNA typing using the AmpFlSTR profiler PCR amplification kit.

Frequency data for nine short tandem repeat (STR) loci were collected from 130 unrelated Caucasians from North Bavaria using the AmpFlSTR Profiler multiplex system. The loci D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, D7S820 and the sex test amelogenin were investigated. Allele frequencies, rates of heterozygosity and the discrimination power of the combined systems were calculated by statistical analysis.

Frequencies of the 5 PCR-based genetic markers LDLR, GYPA, HBGG, D7S8, and GC in a north Bavarian population.

Genotype and allele frequencies for the 5 PCR-based genetic markers LDLR, GYPA, HBGG, D7S8 and GC were determined in a North Bavarian population (n = 150) using a new multiplex PCR-amplification and typing kit. Results did not diverge from Hardy-Weinberg expectations.