Ulrich Abel's research while affiliated with National Center for Tumor Diseases (NCT) Heidelberg and other places

Publications (76)

Article
Background: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). Methods: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-...
Article
Full-text available
Although tumor-initiating cell (TIC) self-renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long-term progression of PDAC in serial xenotransplantation is driven by a succession of transiently a...
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Background Patients with advanced stage non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) often experience multidimensional impairments, affecting quality of life during their course of disease. In lung cancer patients with operable disease, several studies have shown that exercise has a positive impact on quality of life and phys...
Article
Our group has recently shown that human pancreatic cancer (PDAC) progression is driven by a succession of transiently active tumor initiating cell (TIC) clones during serial xenotransplantation. Genetic labeling demonstrated that serial PDAC xenograft tumors and even tumors of parallel mice transplanted with cells from the same donor xenografts har...
Article
Background Pancreatic cancer is mainly a disease of the elderly population, but clinical trials do not reflect this age distribution. Data on treatment strategies and outcome of older patients are limited. The aim of our study was to analyze safety and outcome in elderly patients with advanced pancreatic cancer treated with palliative chemotherapy...
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Full-text available
Aim: The study aimed to evaluate in patients with advanced NSCLC the safety, feasibility and effects of an eight-week combined resistance and endurance exercise program during in- and outpatient care. Methods: In this open, prospective, single-center trial 40 patients with advanced NSCLC received simultaneous or sequential radio-chemotherapy or che...
Article
This study aimed to evaluate safety, feasibility and effects of an eight-week combined resistance and endurance exercise program in patients with advanced NSCLC during in- and outpatient care. In this intervention study, 40 patients with predominantly advanced NSCLC receiving simultaneous or sequential radio-chemotherapy or chemotherapy alone were...
Article
Despite accumulating evidence indicating a pivotal role of tumor-initiating cells (TIC) in tumor progression and metastases formation of pancreatic cancer (PC), very little is known about the clonal TIC dynamics within PC tumors in vivo. It is unclear whether the high aggressiveness of PC is driven by a homogeneous population of self-renewing TIC o...
Article
PURPOSEAdjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study. PATIENTS AND METHODS Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), c...
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The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor m...
Data
Expected values E(cis2) for γ-retroviral distributions. Modeling a more general γ-retroviral distribution of the IS allowing for arbitrary halfwidth w of the intervals ITSS, and including a slight correction. We use the notation and terminology introduced in the Methods section of the manuscript. (DOC)
Data
Technical remarks regarding conditional/unconditional CIS analysis. Differences between the conditional an unconditional CIS analysis for a) uniform IS distribution, b) lentiviral IS distribution, c) γ-retroviral IS distribution. We use the notation and terminology introduced in the Methods section of the manuscript. (DOC)
Article
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Vectors based on γ-retroviruses or lentiviruses have been shown to stably express therapeutical transgenes and effectively cure different hematological diseases. Molecular follow up of the insertional repertoire of gene corrected cells in patients and preclinical animal models revealed different integration preferences in the host genome including...
Data
Formulae for the number of coincidences of IS in different cell types. Two situations were considered: a) No contaminations, b) contaminations do occur. We use the notation and terminology introduced in the Methods section of the manuscript. (DOC)
Data
Expected value E(cis5) for the CIS of order 5 under a uniform distribution of the IS. The resulting formula for CIS of order n = 5 is given. We use the notation and terminology introduced in the Methods section of the manuscript. (DOC)
Article
Human colon cancer harbors a small subfraction of tumor-initiating cells (TICs) that is assumed to be a functionally homogeneous stem-cell-like population driving tumor maintenance and metastasis formation. We found unexpected cellular heterogeneity within the TIC compartment, which contains three types of TICs. Extensively self-renewing long-term...
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Vector-associated side effects in clinical gene therapy have provided insights into the molecular mechanisms of hematopoietic regulation in vivo. Surprisingly, many retrovirus insertion sites (RIS) present in engrafted cells have been found to cluster nonrandomly in close association with specific genes. Our data demonstrate that these genes direct...
Article
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18-Fluorodeoxyglucose-PET (18F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake dete...
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Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration prefere...
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X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein, an adenosine triphosphate–binding cassette transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patien...
Article
The evaluation of diagnostic tests (DT) or procedures is not subject to uniform regulations. However, a thorough evaluation of DT which are intended for use in routine medical practice is advisable or even indispensible for economic, medical, and ethical reasons. This article addresses some important aspects of this evaluation: the facets of "evalu...
Article
Die Bewertung diagnostischer Tests (DT) oder Maßnahmen unterliegt keinen einheitlichen Regularien. Jedoch ist eine gründliche Evaluierung von DT, die für den Einsatz in der medizinischen Routinepraxis vorgesehen sind, aus wirtschaftlichen, medizinischen und ethischen Gründen empfehlenswert beziehungsweise häufig sogar unabdingbar. Der vorliegende B...
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The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II tri...
Article
Fibrin sealant is widely used in almost all fields of surgery and has proved to be an effective therapeutic tool in cardiothoracic surgery. Nevertheless, there have been concerns about early bypass graft occlusion associated with the use of fibrin glue. This analysis has been performed to assess the risks and benefits of Tissucol Duo S in coronary...
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Recent reports have challenged the notion that retroviruses and retroviral vectors integrate randomly into the host genome. These reports pointed to a strong bias toward integration in and near gene coding regions and, for gammaretroviral vectors, around transcription start sites. Here, we report the results obtained from a large-scale mapping of 5...
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We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retro...
Article
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Features such as mutations or structural characteristics can be non-randomly or non-uniformly distributed within a genome. So far, computer simulations were required for statistical inferences on the distribution of sequence motifs. Here, we show that these analyses are possible using an analytical, mathematical approach. For the assessment of non-...
Article
We investigated whether there is a relationship between loss of p16(INK4a) protein expression and p53 alterations in head and neck squamous cell carcinomas (HNSCCs). For this purpose, immunohistochemistry was performed on tissue microarrays of 664 tumours; this represents the largest HNSCC cohort studied for molecular biomarkers. Loss of p16(INK4a)...
Article
Second-line chemotherapy is widely used in advanced pancreatic cancer. However, only few data exist concerning the question who might benefit from second-line therapy. We intended to identify prognostic factors for time to second progression (TTP2) and residual survival following second-line chemotherapy of patients with advanced pancreatic cancer....
Article
Three approaches for constructing exact (test-based) confidence intervals (CIs) for sums of two independent binomial parameters are presented and compared with each other: (1) a method based on rectangular confidence regions - this method is implemented using either Pearson-Clopper CIs or Sterne’s method; (2) CIs based on non-rectangular confidence...
Article
Traditionally, the classification of risk areas of tick-borne encephalitis (TBE) is based on the recording of autochthonous cases of the disease. In Germany, an extension of these areas over the years and an increasing virus prevalence in ticks have been observed in recent years. Registration of foci with autochthonous TBE cases, recording of disea...
Article
This study was designed to investigate the influence of intraoperative and postoperative radiotherapy on functional outcome after rectal resection for rectal cancer. One hundred patients who underwent deep or standard anterior resection for rectal cancer were included in this follow-up study. All patients filled out questionnaires regarding morbidi...
Article
There is an evidence that components of the insulin-like growth factor (IGF)-signaling pathway are involved in the development and progression of prostate cancer. The aim of the present study was to provide a comprehensive analysis of the expression levels of proteins of the IGF axis in prostate cancer. We studied expression of the ligands IGF-I an...
Article
Postoperative surveillance is an important part of the curative therapy of colorectal cancer patients. The effort and effectiveness of these surveillance programs are controversially discussed. We analyzed the practiced follow-up of patients who had undergone a curative resection of colorectal cancer to demonstrate the difficulty to validate the pe...
Article
E-cadherin-mediated and desmosomal cell-cell adhesion have been implicated in the suppression of invasive and metastatic behavior of squamous cell carcinomas. Whether the adhaerens junction represented by E-cadherin and the desmosomes interplay or have distinct and separate roles in squamous cell cancer progression is still unclear. We have studied...
Article
Tumornachsorgeprogramme für kolorektale Karzinome sollen den Nutzen einer kurativen Primärtherapie sichern. Aufwand und Effektivität dieser Nachsorge werden kontrovers diskutiert. Die Analyse der Nachsorgediagnostik an Patienten mit kurativer Resektion eines kolorektalen Karzinoms soll die Problematik beschreiben, die in der Einschätzung der Validi...
Article
Evaluation of the accuracy of descriptive and physiological parameters calculated from signal intensity–time curves using T1-weighted dynamic contrast enhanced MRI (DCE MRI) to differentiate prostate cancers from the peripheral gland. Twenty-seven patients with prostate cancers were examined with DCE MRI prior radical prostatectomy. Regions of inte...
Article
The tumor site is a strong clinical factor in head and neck squamous cell carcinoma (HNSCC). To clarify the biologic and clinical role of p53 alterations in HNSCC, we have examined the prevalence and the nature of p53 alterations in a large cohort of tumors from the different sites. For immunohistochemical analysis of p53 protein expression, we int...
Article
The extreme variability of prostate cancer implies latent disease with missing clinical symptoms in some cases. Tumor suppressors PTEN (phosphatase and tensin homolog deleted on chromosome ten) and p27kip1 are frequently mutated in various human cancers. PTEN negatively influences cell growth and induces apoptosis, while p27kip1 binds to cyclin-E-C...
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Recent Wilms' tumor (WT) trials and studies have tried to determine the minimal therapy needed for cure. The goal was survival without morbidity. From January 1989 to March 1994 the German Society of Pediatric Oncology and Hematology registered 440 patients (median age 2.9 years; 231 male, 209 female) with WTs (preoperative chemotherapy 362) for th...
Article
The progression of clinically manifest premalignant lesions in the head and neck region to primary or second primary cancer is characterized by numerical and structural chromosomal aberrations. However, many tumors arise from histologically inconspicuous mucosal sites. The objective was to investigate whether chromosomal aberrations can be detected...
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AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with t...
Article
Knowledge concerning the prevalence of the tick-borne encephalitis virus (TBEV) in wild living tick populations is very important for understanding the epidemiology of the disease and for immuno prophylactic strategy. In Germany high and low risk areas of TBE exist. In the years 1997-2000, 533 autochthonous clinical TBE cases were recorded, in the...
Article
Full-text available
Histologic subtypes of standard histology Wilms' tumor (WT) and the effect of preoperative therapy on their clinical and histologic features, deserve to be analysed in respect to outcome to find an adequate baseline for therapy. The German Society of Paediatric Oncology & Haematology enrolled patients from January 1989 to March 1994 for therapy acc...
Article
Radiation oncologists are often faced with patients with advanced non-small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the-art radical treatment, but who also are not judged to have a very short life expectancy. Some physicians treat these patients palliatively, whereas others advocate more intensive treatment. To find o...
Article
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagno...
Article
The prevalence of tick-borne encephalitis virus (TBEV) in Ixodes ricinus tick populations in endemic areas of Germany with the highest TBE risk is unknown. Annual and seasonal differences in TBEV prevalence have also not been studied. Against this background, in May 1997 we started a systematic virus surveillance programme in ticks collected in loc...
Article
A major problem for children receiving Wilms tumor (WT) chemotherapy is hepatotoxicity, which may even be life-threatening. Dactinomycin (AMD) has been shown to be an important factor, as has abdominal irradiation. In the nephroblastoma trial and study SIOP-9 (SIOP-9) two different regimens for the application of AMD were used (standard dose over 3...
Article
Pooled testing of units is a common approach in the prevalence estimation of infectious agents, which leads to a reduction of total costs of diagnostic testing. We examine how the pool size affects the statistical properties of the prevalence estimator r. Exact formulae are used to determine bias and precision of r. It is shown that with moderate p...
Article
BackgroundA major problem for children receiving Wilms tumor (WT) chemotherapy is hepatotoxicity, which may even be life-threatening. Dactinomycin (AMD) has been shown to be an important factor, as has abdominal irradiation.ProcedureIn the nephroblastoma trial and study SIOP-9 (SIOP-9) two different regimens for the application of AMD were used (st...
Article
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagno...
Article
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. □ Following recent methodological research German biostatisticians usually distinguish between 4 types of diag...
Article
On the basis of a survey of the methodological literature, we analyze widespread views on randomization and the advantage of randomized over nonrandomized studies. These views follow from theoretical considerations and at least three types of empirical investigations into the results of published studies. Randomization is often credited with advant...
Article
The evaluation of diagnostic tests play an important role in clinical research. Though detailed standards have been developed for treatment evaluation, widely accepted methodological standards in diagnostic test research are still lacking. Following recent methodological research German biostatisticians usually distinguish between 4 types of diagno...
Article
We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. Cervical spinal...
Article
Unter Randomisierung (random=zufällig) versteht man die zufällige Zuweisung von Patienten zu einer von mindestens 2 zu vergleichenden Therapiegruppen. Die Randomisierung gilt als state of the art besonders für Therapiestudien. Wichtige Voraussetzung ist, daß aus ärztlicher Sicht keine der Therapien den anderen überlegen ist. Eine randomisierte Stud...
Article
In a prospective randomized trial we examined whether radiotherapy of painful bone metastases can be shortened using larger single doses without impairing effectivity. One hundred patients with painful bone metastases having no prior surgical intervention or treatment with x-ray therapy and had a median follow-up of 12 months were analyzed. The pri...
Article
In order to avoid overtreatment in advanced NSCLC we developed a palliative accelerated irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a 1-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conve...

Citations

... cetuximab-based therapy (4 week) for mCRC, the innovative principle based on any eligible VOI more than 2 could ahead of this schedule after one week (50). And the early metabolic response based on the reduction of SUVmax more than 20%, fitted with EORTC criteria (51), could serve as the surrogate parameter for early clinical response under cetuximab in CRC patients (52). All cases reviewed here are summarized in Table 2. ...
... Immunohistochemistry for p16 was performed according to the antibody protocol of the automated Omnis immunohistology system (Agilent DAKO, Santa Clara, CA, United States) using an mouse-anti-p16 primary antibody, JC2, 1:50 (ZETA Corporation, Agilent), an HRP-conjugated secondary antibody, and DAB chromogen. Indirect immunofluorescence staining of tumor tissue was performed as described previously [18,19]. Primary antibodies: rabbit-anti-ALDH1A1, 20H2L4, 1:100 (Thermo Fisher Scientific, Waltham, MA, United States), rabbit-anti-CD3, SP7, 1:100 (Novus Biologicals, Centennial, CO, United States), mouse-anti CD20, FMC63, 1:100 (Novus Biologicals), mouse-anti-FOXP3, 2A11G9, 1:100 (Santa Cruz Biotechnology Inc., Dallas, TX, United States). ...
... Studies have shown that physical activity can produce a series of benefits for lung cancer patients, which can improve the cardiopulmonary and fatigue status of lung cancer patients, and improve the survival rate [20,21]. We reduce physical and mental fatigue, reduce anxiety, increase cognitive function, improve selfesteem, increase muscle tone and balance, help weight control, enhance immune system, improve sleep, improve quality of life, etc. [22][23][24]. e American College of Sports Medicine (ACSM) recommends that cancer patients do at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity exercise per week [25]. In view of the fact that the level of physical activity of patients undergoing lung cancer surgery needs to be improved, medical staff and patients should pay more attention to physical activity and formulate a reasonable exercise program according to the specific situation of the patient to improve the physical activity level of the patient. ...
... However, gene therapy can also be applied to reprogramming cells in contexts other than inherited diseases [44], one of which is PNI. Following decades of research and limited efficacy, gene therapy has recently entered a ''golden era'' with a range of high-profile life-saving clinical trials for hematological [45], immunological [46,47], ophthalmic [48], and neurological conditions [49,50]. These advances may become relevant to translational research in gene therapy to promote peripheral nerve repair. ...
... Intermediate radiation doses of between 30 and 60 Gy, such as the Norwegian CONRAD regime (42 Gy in 15 fractions) (7), are endorsed in current guidelines (8), preferably in combination with platinum-based chemotherapy. In clinical practice of palliative radiotherapy, OAR contouring and prioritization, as well as treatment delivery technique vary between institutions (9)(10)(11)(12). In order to study the radiotherapy heart dose in a real-world practice setting, we performed a retrospective analysis of patients who received palliative radio-or chemoradiotherapy. ...
... The time between collection of live ticks and storage at ) 80°C was no longer than 24-48 h. Field-collected ticks were pooled into groups of mainly five male or female adults, 10 nymphs or 20 larvae, depending on the estimated prevalence of TBE in the examined region [11]. ...
... It is foreseeable that its incidence will increase with the accelerating aging process. Elderly patients generally have a worse prognosis than younger patients due to their poor conditions and comorbidities [8,9]. Even for those with good physical conditions, factors such as age and postoperative complications may prevent them from receiving more radical treatments [10]. ...
... So, it is of great importance that to identify molecular events and key factors that can determine or predict the behaviors of the tumor (10). For this purpose, genetic factors related to the prognosis of prostate cancer was investigated in many studies (11)(12)(13). Also, the genetic background and family history are related to a growing incidance of prostate cancer (14,15). ...
... However, the molecule that could play a key role in mediating all of the positive anti-inflammatory effects induced by physical activity is the Mitogen Activated Protein Kinase (MAPK). This fuel-sensing enzyme, activated in contracting skeletal muscles, stimulates energy-generating pathways such as glycolysis and fatty acid oxidation, and decreases energy-consuming processes such as protein and lipid biosynthesis [52]. Physical activity mediated MAPK signaling accomplishes a dual purpose: it activates energy metabolism and can indirectly inhibit the inflammatory response induced by the NF-κB associated with chronic stress, likewise occurring in metabolic and inflammatory syndrome as well as in type 2 diabetes, obesity, and cancer [48,51]. ...
... In general, we can distinguish four phases for diagnostic and prognostic biomarker studies (q Table 2) [1,[8][9][10][11][12]. Phase I comprises preliminary technical and methodological studies. ...