Andreas-Claudius Hoffmann

KMG Klinik Silbermühle GmbH · Hematology & Oncology

Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the progn...

Background: Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic...

Background: With over 600,000 newly diagnosed hepatocellular cancer (HCC) patients worldwide every year and ongoing clinical research, it is surprising that many of the new molecular entities have not yet resulted in significant prolongation of progression-free or overall survival. Nevertheless, there are a number of promising agents currently und...

Purpose: Due to their minimal-invasive yet potentially current character circulating tumor cells (CTC) might be useful as a "liquid biopsy" in solid tumors. However, successful application in metastatic renal cell carcinoma (mRCC) has been very limited so far. High plasticity and heterogeneity of CTC morphology challenges currently available enric...

Background: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, pr...

[This corrects the article DOI: 10.1371/journal.pone.0054193.].

Purpose: Standardized computer-aided tumor response assessment is common in clinical trials. In contrast, unstructured free text reporting (UFTR) is common in daily routine. Therefore, this study aimed to discern and quantify differences between UFTR and computer-aided standardized tumor response evaluation based on RECIST 1.1 criteria (RECIST), s...

Context and objective: Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics. Methods and results: Proteomic differences between HCC and nontumorous liver tissue were studied by...

Flowcytometric immunophenotyping. Flowcytometric analysis and validation of the CD133 cell surface expression on K562 cells engineered to express the CD133 splice variant s1 encoded by an IRES-eGFP expression cassette (CD133:IEG). Cells were stained with PE-conjugated isotype control or anti-CD133 antibodies. (TIF)

The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infecti...

Aims: The distinction between intrahepatic cholangiocarcinoma (ICC) and benign bile duct lesions can be challenging. Using our previously identified potential biomarkers for ICC, we examined whether these are useful for the differential diagnosis of ICC, bile duct adenoma and reactive bile duct proliferations in an immunohistochemical approach and...

Purpose: Lung cancer accounts for one in five cancer deaths. Broad screening strategies for high-risk populations are unavailable, and the validation of biomarkers for early cancer detection remains a prime interest. Therefore, we investigated the value of circulating U2 small nuclear RNA fragments (RNU2-1f) as a biomarker for diagnosis, prognosis...

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing for an accurate and early tumor diagnosis. To identify potential markers with such applications, we analyzed a patient cohort consisting of 50 pat...

The exact discrimination of lesions with true hepatocellular differentiation from secondary tumours and neoplasms with hepatocellular histomorphology like hepatoid adenocarcinomas (HAC) is crucial. Therefore, we aimed to identify ancillary protein-biomarkers by using complementary proteomic techniques (2D-DIGE, label-free MS). The identified candid...

Allogeneic hematopoietic stem cell transplantation (AHSCT) has been shown to provide longterm disease-free survival for otherwise fatal malignant or nonmalignant hematological disorders. Acute and chronic graft-versus-host disease (aGvHD and cGvHD) are a major complication following AHSCT and are associated with a substantial morbidity and mortalit...

Hepatic fibrosis and cirrhosis are major health problems worldwide. Up to now, highly invasive biopsy remains the diagnostic gold standard despite many disadvantages. In order to develop non-invasive diagnostic assays for the assessment of liver fibrosis it is urgently necessary to identify molecules which are robustly expressed in association with...

Since image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hem...

BACKGROUND & PURPOSE: Hepatocellular carcinoma (HCC) is a major lethal cancer worldwide. Despite sophisticated diagnostic algorithms, the differential diagnosis of small liver nodules still is difficult. While imaging techniques have advanced, adjuvant protein-biomarkers as glypican3 (GPC3), glutamine-synthetase (GS) and heat-shock protein 70 (HSP...

The aim of this study was the identification of novel biomarker candidates for the diagnosis of cholangiocellular carcinoma (CCC) and its immunohistochemical differentiation from benign liver and bile duct cells. CCC is a primary cancer which arises from the epithelial cells of bile ducts and is characterised by high mortality rates due to its late...

Circulating tumor cells (CTC) and cancer stem cells (CSC) have been proposed as tools for detection and characterization of disease and individualization of therapy in patients with many solid tumors. Several automated and semi-automated techniques for identification and isolation of these cells from blood have been proposed and reviewed mostly foc...

Background: Local ablative techniques such as selective internal radiation therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma (HCC) in the bridging-to-transplant and palliative setting. We recently demonstrated that epithelial circulating tumor cells (CTCs) correlate to an unfavorable outcome. We wanted to scrutinize whet...

Circulating tumor cells (CTC) could serve as a "liquid biopsy" for individualizing and monitoring treatment in patients with solid tumors as recently shown by our group. We assessed which non-hematopoietic cell types are identifiable in the peripheral blood of patients with non-small cell lung cancer (NSCLC) and correlated those to clinical charact...

Circulating tumor cells (CTCs) have been proposed as a monitoring tool in patients with solid tumors. So far, automated approaches are challenged by the cellular heterogeneity of CTC, especially the epithelial-mesenchymal transition. Recently, Yu and colleagues showed that shifts in these cell populations correlated with response and progression, r...

Background Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients w...

Multi-OMICS approaches aim on the integration of quantitative data obtained for different biological molecules in order to understand their interrelation and the functioning of larger systems. This paper deals with several data integration and data processing issues that frequently occur within this context. To this end, the data processing workflo...

Proteomics-based clinical studies have been shown to be promising strategies for the discovery of novel biomarkers of a particular disease. Here, we present a study of hepatocellular carcinoma (HCC) that combines complementary gel-based and LC-MS-based approaches of quantitative proteomics. In our proteomic experiments, we analyzed a set of 14 samp...

Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. An isogenic model of cisplatin resistance was generated in a...

2086 Background: Deregulation of the PI3K/AKT pathway has been preclinically involved in the pathophysiology of GBM. The mammalian target of rapamycin (mTOR) is an important downstream mediator of PI3K/AKT signalling. The mTOR-inhibitor temsirolimus (Tem) achieves significant drug levels in brain. Thus, Tem may be effectively combined with irinotec...

Background: Using liver-derived circulating tumor cells (CTC) as “liquid biopsy” may be a promising approach for individualizing and monitoring treatment in patients with HCC. However, this is challenged by cellular heterogeneity. Therefore, we wanted to assess whether CTC subtypes are identifiable in the peripheral blood of patients with HCC and w...

To evaluate feasibility, safety, efficacy as well as acute and short-term outcome of hemodynamically supported percutaneous coronary intervention (PCI) by a percutaneous, catheter-based left ventricular assist device (LVAD) (Impella LP 2.5, Abiomed Europe GmbH, Aachen, Germany) in a high-risk patient population with acute coronary syndrome. Althoug...

s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Background: There is no effective systemic therapy for patients (pts) with metastatic uveal melanoma (metUvMel). Due to the paucity of clinical trials pts are frequently offered individual treatment options. We have analyzed th...

226 Background: Cholangiocellular carcinoma (CCC) remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of VEGF receptor 1 (VEGFR1), heparanase (HPSE) and EGF receptor (EGFR) gene expression in patients with resected CCC. Methods: 47 formallin-fixed paraffin embedded F...

PURPOSE: The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair crosscomplementing 1 (ERCC1) may help identify the group of patients benefiting from...

The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair cross-complementing 1 (ERCC1) may help identify the group of patients benefiting from cisplat...

7512 Background: ERCC-1 is a nucleotide excision repair gene associated with DNA repair of DNA adducts induced by platinum based chemotherapy. ERCC-1 mRNA levels have been shown to predict response in patients with NSCLC when treated with platinum based chemotherapy. We therefore examined whether ERCC1 expression levels in specifically enriched cir...

Survivin (SVV) mRNA expression levels in peripheral blood of patients with gastrointestinal malignancies change significantly during the course of treatment. We wanted to scrutinize these findings in patients with esophageal carcinoma and furthermore evaluate whether the detection of mRNA and the change in detecting ability have an association with...

Since their introduction more than 50 years by Engell, circulating tumor cells (CTCs) have been evaluated in cancer patients and their detection has been correlated with clinical outcome, in esophageal, gastric, and colorectal cancer. With the availability of refined technologies, the identification of CTCs from peripheral blood is emerging as a us...

Zusammenfassung In den letzten Jahren wurde durch Grundlagenforschung und translationale Forschung in der Onkologie eine Reihe von Biomarkern identifiziert, die für Diagnostik, Staging, Prognoseabschätzung und als Ansatzpunkte für individualisierte Therapien potentiellen klinischen Wert haben. Einige dieser Marker sind bereits in die klinische Prax...

Analysis of survivin RNA expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus. Blood samples were drawn from 29 patients with esophageal cancer prior to neoadjuvant radiochemotherapy. After extraction of cellular tumor-RNA from blo...

To further improve the screening, diagnosis and therapy of patients with non-small cell lung cancer (NSCLC) additional diagnostic tools are desperately warranted. Aim of this study was to investigate the potential of the DNA methylation of DAPK, MGMT, and GSTPI in serum of patients with NSCLC as a prognostic molecular marker in this disease. Sevent...

Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a (HIF1a), heparin-binding epidermal growth factor-like gro...

DPD and TS expression have been shown to correlate with response of 5-FU based chemotherapy in colorectal cancer tissue. Little is known about mRNA expression levels of TS and DPD in peripheral blood. The goals of this study were to test the feasibility of DPD and TS detection in blood and their associations to TNM staging and complete surgical res...

Death-associated protein kinase (DAPK) and adenomatous polyposis coli gene (APC) have been recently shown to be associated with outcome in patients with esophageal carcinoma, especially adenocarcinoma. We wanted to validate the correlation of these two markers with outcome by detecting methylated DNA sequences in peripheral blood. Circulating cell-...

e22081 Background: The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp), whose function is the energy dependent export of substances from the inside of cells, and from membranes, to the outside. MDR1 mRNA levels have been shown to influence metabolism of cancer drugs. We tested whether MDR1 gene expression is associated wi...

5026 Background: The human MDR1 gene encodes an integral membrane protein, P glycoprotein (Pgp), whose function is the energy dependent export of substances from the inside of cells, and from membranes, to the outside. MDR1 mRNA levels have been shown to influence metabolism of cancer drugs. We tested whether MDR1 gene expression is associated with...

Background: Although circulating tumor DNA has been detected in patients with different types of cancer, less is known about free RNA in cancer patients. Therefore, we evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with esophageal cancer. Furthermore...

Grundlagenforschung und translationale Forschung in der Onkologie konnten in den letzten Jahren eine Reihe von Biomarker identifizieren, die für Diagnostik, Staging, Prognoseabschätzung und als Ansatzpunkte für individualisierte Therapien potentiellen klinischen Wert haben. Einige dieser Marker sind bereits seit Jahren in die klinische Praxis einge...

The aim of this study was to determine the gene is spelled excision repair cross-complementing gene 1 (ERCC1) RNA-expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radio-chemotherapy in patients with locally advanced cancer of the esophagus. Only patients with locally advanced cancer of the esophagus wi...

Pancreatic cancer still has one of the worst prognoses of all cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. Especially heparanase (HPSE) has recently been discus...

Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis associated with locally advanced esophageal cancer. However, only patients with a major histopathologic response to neoadjuvant therapy will have a significant survival benefit. Predictive markers to allow individualization of multimodality treatment could be ve...

4503 Background: Surgery is the first line treatment for patients with resectable pancreatic ductal adenocarcinoma (PDA). However pancreaticoduodenectomy is challenging and some patients recur quickly, negating the benefit of aggressive resection. To assess for prognostic information in resected tissues, we compared gene expression profiles associa...

4131 Background: ERCC-1 is a nucleotide excision repair gene associated with DNA repair of DNA adducts induced by platinum based chemotherapy. ERCC-1 mRNA levels have been shown to predict outcome in patients with NSCLC, gastric, bladder and ovarian cancer when treated with platinum based chemotherapy. We tested whether ERCC-1 gene expression is as...

5564 Background: The excision repair cross-complementation group 1 (ERCC1) enzyme is a crucial component of the nucleotide excision repair pathway which removes cisplatin-induced DNA adducts. High ERCC1 mRNA expression has been associated with platinum resistance in several tumor types. We assessed the relationship between ERCC1 expression and surv...