Jan Brabender's research while affiliated with St.-Antonius-Hospital Eschweiler and other places

Publications (166)

Article
The prognostic value of TS (thymidylate synthase) and DPD (dihydropyrimidine dehydrogenase) RNA expression in the blood of patients with esophageal cancer is not known. The aim of the present study was to evaluate the significance of these molecular alterations in the blood as a prognostic marker for patients with neoadjuvant-treated esophageal can...
Article
Background KRAS mutations are associated with diverse biologic functions as well as prognostic and predictive impact in non-small cell-lung cancer (NSCLC) and colorectal cancer (CRC). In CRC, benefit from monoclonal antibody therapies targeting EGFR is generally limited to patients whose tumors have wild-type (WT) KRAS, whereas data suggest that th...
Article
In order to identify possible predictive markers, this study aimed to characterize miRNA profiles of responder and non-responder in the multimodality therapy of locally advanced esophageal cancer. Initially a microarray-based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followe...
Article
The aim of this study was to investigate the relevance of mRNA expression and DNA methylation of GST-PI in tumor and non-tumor lung tissue from NSCLC patients in terms of prognostic and pathogenetic value of this biomarker. Quantitative real-time PCR was used to measure mRNA expression and DNA methylation of GST-PI in paired tumor (T) and non-tumor...
Article
Neoadjuvant treatment options have been developed to improve survival of patients with locally advanced rectal cancer. As only patients with a major histopatholocial response benefit from this preoperative therapy, several tumor regression grading systems have been developed. However, currently no accepted comprehensive grading system for clinical...
Article
Aims/hypothesis: Pathological cardiac hypertrophy is an early phenotype in both types 1 and 2 diabetes. The primary stimulus for hypertrophic growth in diabetes is yet unknown and may involve neurohumoral stimulation of Gq-coupled receptors as well as direct glucose-dependent mechanisms. To discriminate between these hypertrophic stimuli we analyz...
Article
Limited data suggest that extracapsular lymph node involvement (LNI) has a negative prognostic impact in gastrointestinal malignancies. The aim of this study was to assess the prevalence and prognostic impact of LNI in patients with primary resected rectal cancer. Between 1997 and 2007, 243 rectal cancer patients underwent surgical therapy without...
Article
Despite of improvements in detection, surgical techniques and intensive care medicine, esophageal perforation remains a potentially fatal disease with mortality rates of in up to 40%. Therefore, a quick diagnostic work-up and an effective therapeutic management in order to eliminate the septic focus with sufficient drainage of the mediastinum is of...
Article
Thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) RNA expression in peripheral blood was examined as a noninvasive 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 (10 squamous cell carcinom...
Article
Neoadjuvant radiochemotherapy (RT/CTx) regimens were primarily designed for treatment of squamous cell carcinoma of the esophagus. Own preliminary results demonstrate that also patients with locally advanced adenocarcinoma of the esophagus may achieve a major response in 30% with a 3-year survival rate of 80%. To identify these patients, ERCC1 (rs1...
Article
Despite improvements in preoperative staging, surgical techniques and postoperative care, the 5-year survival rate of patients with locally advanced esophageal cancer remains only approximately 15-40%. Therefore, multimodality treatment options have been widely promoted in the therapy of this malignant disease. However, recent meta-analyses evaluat...
Article
microRNAs (miRNAs) are small non-coding RNAs with important post-transcriptional regulatory functions. miRNA-21 (miR-21) is upregulated and miR-143 and miR-145 are downregulated in colorectal carcinoma. The aim of our study was to determine if these miRNAs change their expression levels in response to neoadjuvant chemoradiotherapy in advanced recta...
Article
Multimodality treatment options have been widely promoted in the therapy for locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy and combined radiochemotherapy are frequently used in this setting. The recent meta-analyses evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery for patie...
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Full-text available
To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for th...
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Full-text available
Neoadjuvant treatment strategies have been developed to improve survival of patients with advanced rectal cancer. Since mainly patients with major histopathological response benefit from this therapy, predictive and prognostic markers are needed. We examined the association of β-catenin and Her2/neu protein expression with histopathologic response...
Article
ZusammenfassungDie beste therapeutische Option in der Therapie des Barrett-Adenokarzinoms besteht in der Entfernung des Primärtumors und seiner regionalen Lymphknotenmetastasen, sofern eine komplette Resektion ohne Residualtumor erreicht werden kann. Das Operationsverfahren der Wahl ab einer Tumorinfiltration der Submukosa ist die subtotale Enbloc-...
Article
Neoadjuvant treatment strategies have been developed to improve the survival of patients with locally advanced esophageal cancer. Since patients with major histopathological response are the ones who mainly benefit from this therapy, we are looking for causes of nonresponse. The multidrug resistance protein ABCB1 belongs to the ATP-binding cassette...
Article
Full-text available
We evaluated the outcome of primarily resected rectal cancer patients immediately after the implementation of total meserectal excision (TME) based on potential quality indicators. Following initial teaching of two staff surgeons (PMS and AHH) by RJ Heald, 164 consecutive patients were analyzed. The following quality indicators were evaluated: (a)...
Article
Neoadjuvant treatment strategies have been developed to improve survival of patients with locally advanced rectal cancer. Since mainly patients with major histopathologic response benefit from this therapy, predictive markers are needed. The gene polymorphism of the X-ray-repair-cross complementing (XRCC1-) gene (rs25487) was analyzed to predict re...
Article
The effect of the apoptosis related gene Bcl-2 in the pathogenesis in NSCLC remains poorly investigated. Hence the aim of this study was to explore the potential role of Bcl-2 mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC. 91 tumor and matching normal tissue samples from patients with NSCLC were analyzed using...
Article
Thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydropyrimidine dehydrogenase (DPD) are key enzymes in the 5-fluorouracil (5-FU) pathway. The aim of this study was to investigate the mRNA expression of TS, TP, and DPD in tumor and nontumor lung tissue of patients with NSCLC and to determine the potential of these genes as molecular b...
Article
Einleitung: Anastomoseninsufffizienzen des Osophagus nach Osophagektomie bzw. Gastrektomie gehen mit einer hohen Mortalitat und Morbiditat einher und bedurfen der umgehenden Therapie. Therapeutisch kommt ein konservatives oder chirurgisches Vorgehen in Betracht. Wir berichten hier uber unsere Erfahrungen mit der Behandlung von Insuffizienzen durch...
Article
Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocar...
Article
10522 Background: Targeted treatment strategies have been developed to improve survival of patients (pts) with metastatic colorectal cancer. Vatalanib (PTK787/ZK 222584) is an oral angiogenesis inhibitor and was combined with FOLFOX in first- (CONFIRM 1) and in second line (CONFIRM 2) but did not significantly improve progression-free survival or o...
Article
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...
Article
The effect of ornithine decarboxylase (ODC) on the pathogenesis of non-small-cell lung cancer (NSCLC) remains poorly investigated. Hence, the aim of this study was to explore the potential role of ODC mRNA expression as a prognostic biomarker in patients with curatively resected NSCLC. A total of 91 tumor and matching nontumorous lung tissue sample...
Chapter
Introduction: Neoadjuvant radiochemotherapy (RT/CTx) regimens were primarily designed for treatment of squamous cell carcinoma (SCC) of the esophagus. Own results demonstrate that also patients with locally advanced adenocarcinoma (AC) of the esophagus may achieve a major response in 30 % with a 3 year survival rate of 80 %. To identify these patie...
Article
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...
Article
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...
Article
Esophageal adenocarcinoma is the most rapidly increasing cancer in Western countries. Like esophageal squamous-cell carcinoma, these tumors are often detected at an advanced stage, requiring a multimodal concept. Despite improvements in detection, surgical resection, and (neo-) adjuvant therapy, the overall survival of esophageal cancer remains low...
Article
Neoadjuvant therapy is applied to improve the prognosis associated with advanced gastric cancer. Only patients with a major response seem to have a survival benefit. Predictive markers to allow individualisation of treatment could be helpful. We examined the association of survivin protein expression with histopathologic response to neoadjuvant che...
Article
e15520 Background: Neoadjuvant therapy followed by surgery is frequently applied to improve the prognosis of patients with esophageal cancer. However, only a major histopathological response will provide a survival benefit. On the other hand, evidence suggests that patients with response to chemoradiation have no additional benefit from surgery com...
Article
Introduction: ERCC1 is a key enzyme of the nucleotide excision and repair (NER) complex to prevent DNA inter-and intrastrand crosslinks. Genetic alterations of ERCC1 gene are involved in the development and progression of gastrointestinal tumors. We analyzed the prognostic impact of ERCC1 gene polymorphisms in gastric cancer. Methods: There were 11...
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Full-text available
The role of the homeobox genes Backfoot (BFT) and caudal-related Homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The goal of this study was to investigate the mRNA expression of BFT and CDX2 in NSCLC and to determine the association with the pathogenesis and the potential as a biomarker of this disease. The m...
Article
The purpose of this study was to evaluate the significance of human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity as prognostic markers in non-small cell lung cancer (NSCLC). In a series of 69 curatively resected NSCLC specimens, telomerase activity was analyzed with the telomeric repeat amplification protocol (TR...
Article
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...
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Full-text available
Recent studies have shown an association between the GNAS1 T393C polymorphism and clinical outcome for various solid tumors. In this study, we genotyped 51 patients from an observational trial on cisplatin/5-FU-based neoadjuvant radiochemotherapy of locally advanced esophageal cancer (cT2-4, Nx, M0) and genotyping was correlated with histomorpholog...
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Full-text available
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-...
Article
The oxygen-regulated transcription factor subunit hypoxia inducible factor-1alpha (HIF-1alpha) is involved in angiogenesis, energy metabolism, cell survival, and inflammation. We examined the protein expression of HIF-1alpha within the progression of Barrett's sequence as well as the type and degree of the environmental inflammatory reaction. Squam...
Article
Leaks of the esophagus are associated with a high mortality rate and need to be treated as soon as possible. Therapeutic options are surgical repair or resection or conservative management with cessation of oral intake and antibiotic therapy. We evaluated an alternative approach that uses self-expandable metallic stents (SEMS). Between 2002 and 200...
Article
Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis. Hypothetically, methylation resulting in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation. Accordingly, our aim was to investigate if aberrant methylation of the apoptosis-...
Chapter
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...
Article
Full-text available
Background. To further improve the screening, diagnosis, and therapy of patients with nonsmall cell lung cancer (NSCLC) additional diagnostic tools are urgently needed. Gene expression of Cyclooxygenase-2 (COX-2) has been linked to prognosis in patients with NSCLC. The role of the COX-2 926G>C Single Nucleotide Polymorphism (SNP) in patients with N...
Chapter
Currently, esophageal adenocarcinoma is the most rapidly increasing cancer in the Western world. As well as squamous-cell carcinoma of the esophagus, these tumors are frequently detected at an advanced stage, requiring a multimodal concept. Even with improvements in detection, surgical resection and (neo-) adjuvant therapy, the overall survival of...
Article
Objective: To prospectively assess the sensitivity (sens), specificity (spec), positive predictive value (ppv), negative predictive value (npv), and accuracy (acc) for clinical response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound (EUS) to determine histomorphologic regression UICC T-category downstaging after neoadjuvant chemoradia...
Article
We present the successful management of an esophageal perforation after aortic arch aneurysm replacement in a 64-year-old patient. Four weeks after surgical repair of a perforated aortic arch aneurysm, a contained perforation of the thoracic esophagus on the prosthesis was detected. A subtotal esophagectomy and reconstruction by pull-up of the stom...
Article
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...
Article
Predicting the malignant potential of gastrointestinal stromal tumors (GISTs) remains difficult. We assessed the value of serosal penetration, an established prognostic factor in solid tumors, to determine the clinical outcome in patients with GISTs. From 1996-2002, 25 consecutive patients with GIST underwent surgical resection at our Department. T...
Article
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...
Article
Full-text available
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...
Article
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Little is known about its molecular pathogenesis and the relevance of DNA methylation for disease initiation and progression. Nevertheless, promoter methylation of some genes has been implicated as potential marker for HCC. Thirty-four HCC, 34 matching non-malignant, cirrho...
Article
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...
Article
Evidence suggests a significant difference in the incidence, presentation, and outcome of young and elderly patients with esophageal adenocarcinoma. We aimed to compare clinicopathologic and prognostic factors of young and elderly patients with esophageal adenocarcinoma at a surgical department in Europe. From 1996 to 2006, 223 patients with a rese...
Article
Background Asymptomatic diabetic patients have a high incidence of clinically unrecognized left ventricular dysfunction with an abnormal cardiac response to exercise. We, therefore, examined subclinical defects in the contraction-relaxation cycle and intracellular Ca(2+) regulation in myocardium of asymptomatic type 2 diabetic patients. Methods Alt...
Chapter
Background: Only patients with locally advanced cancer of the esophagus with a major histopathological response to neadjuvant radio-chemotherapy benefit from this treatment. Unfortunately, no non-invasive molecular marker exists that can reliably predict response or non-response to neadjuvant therapy in this disease. To further improve the treatmen...