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H Scherübl

Publications and source records attributed to H Scherübl.

At least 19 recordsLinked to original sources
PubMed2006

[Increased incidence of hepatocellular and intrahepatic cholangiocellular carcinoma in northeast Germany].

BACKGROUND AND OBJECTIVE: Hepatocellular cancer (HCC) is one of the five most common cancers worldwide. In Western countries the incidence of both HCC and intrahepatic cholangiocellular cancer (iCCC) has increased quite dramatically in the last 20 years. It was the aim of this study to assess the epidemiological changes of both cancers in the Northeast of Germany. METHODS: Using the data base of the Joint German Cancer Registry of the New Federal States and of Berlin, the age- and world-population-adjusted incidence of HCC and iCCC and their 5-year survival were calculated. The states of Brandenburg, Mecklenburg-Vorpommern and Saxony were chosen for this study because of the high quality of their registration base. RESULTS: In men the age-adjusted incidence of HCC increased from 3.6 in 1976 to 5.7 in 2002, the absolute number of newly diagnosed HCCs rising from 192 to 383 males within this period. In women the incidence was much lower. While only 30 males and 36 females were diagnosed with iCCC in 1976, in 2002 there were 64 men and 75 women with iCCC. In 1976, the corresponding age-adjusted incidence was 0.5 in men and 0.4 in women. Up to 2002 the incidence of iCCC rose to 0.8 and 0.6, respectively. The cumulative 5-year survival of HCC and iCCC was less than 10% for each. Comparison of the early period (1978-1979) with the later one (1998-1999) demonstrated a statistically significant improvement in survival for HCC. This was most likely due to earlier diagnosis and treatment of HCC. CONCLUSION: In the Northeast of Germany the incidence of both HCC and iCCC have increased markedly in the last 20 years. The recently improved survival of HCC patients most likely reflects earlier diagnosis and treatment.

Adult↗
PubMed2004

[Current diagnosis and therapy of esophageal carcinoma].

In Germany the incidence of esophageal cancer is 6 - 10 per 100,000. At the time of diagnosis about 75 % of the patients suffer from UICC stage III or IV esophageal cancer. Less than 10 % of patients are diagnosed with early (T1) cancer. Diagnosis and staging relies on esophagoscopy including biopsies, endoscopic ultrasonography, and computerized tomography of the chest and abdomen. Intramucosal early cancer (T1a) and high-grade dysplasia can be treated either by surgery or by endoscopic mucosal resection. Chemoradiation is the definitive treatment of choice for localized squamous cell cancer of the proximal esophagus. As far as overall survival is concerned definitive chemoradiation is not inferior to esophagectomy even in patients with localized squamous cell cancer of the middle or lower esophagus. In case of high surgical risk chemoradiation should be offered to those patients as the therapy of choice. Esophagectomy should be performed in operable patients suffering from resectable adenocarcinoma of the esophagus. Preoperative chemoradiation is recommended in locally advanced (non-resectable) adenocarcinoma. If staging reveals distant metastases, palliative therapy is indicated. Palliative chemotherapy with 5-fluorouracil and cisplatin should be offered to patients with good performance status. Esophageal intubation (with expandable metal stents) is the palliative treatment of choice for firm stenosing, non-resectable tumors, where rapid relief of dysphagia is required.

Adenocarcinoma↗
PubMed2004

Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer.

Cancers of the esophagus and stomach constitute a major cause of cancer deaths worldwide. Despite improvements in both surgical techniques and (radio) chemotherapy regimens, these tumors remain a great therapeutic challenge. Thus, there is a need for innovative medical treatment strategies effective even in advanced disease. An emerging understanding of the molecular events that characterize carcinogenesis, tumor growth and spread may provide novel targets in cancer therapy. In this review we discuss novel strategies to inhibit growth, angiogenesis, invasion, and spread of tumors and to induce apoptosis. Therapeutic strategies discussed include agents targeting the epidermal growth factor receptor (EGFR) family, the mitogen-activated protein kinase (MAPK) pathway, regulators of apoptosis (NF-kappaB, bcl-2, and the peripheral benzodiazepine receptor), cyclooxygenase-2, the vascular-endothelial growth factor receptor and matrix metalloproteinases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839).

Therapeutic options to inhibit the growth and spread of neuroendocrine (NE) gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of epidermal growth factor receptor-sensitive tyrosine kinase (EGFR-TK), had been shown to suppress potently the growth of various non-NE tumour entities, we studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells and in NE tumour cells of the gut (STC-1), gefitinib induced a time- and dose-dependent growth inhibition by almost 100%. The antiproliferative potency of gefitinib correlated with the proliferation rate of the tumour cells. So the IC(50) value of gefitinib was 4.7+/-0.6 microM in the fast-growing CM cells, still 16.8+/-0.4 microM in the moderate-growing BON cells, and up to 31.5+/-2.5 microM in the slow-growing STC-1 cells. Similarly, the induction of apoptosis and cell-cycle arrest by gefitinib differed according to growth characteristics: fast-growing CM cells displayed a strong G0/G1 arrest in response to gefitinib, while no significant cell-cycle alterations were seen in the slow-growing STC-1. Vice versa, the proapoptotic effects of gefitinib, as determined by caspase-3 activation and DNA fragmentation, were most pronounced in the slow-growing STC-1 cells. Using cDNA microarrays, we found extensive changes in the expression of genes involved in the regulation of apoptosis and cell cycle after incubation with gefitinib. Among them, an upregulation of the growth arrest and DNA damage-inducible gene GADD153 was observed. Phosphorylation of ERK1/2, which inhibits GADD153 expression, was reduced in a time-dependent manner. However, no gefitinib-induced activation of the GADD153-inducing p38 mitogen-activated protein kinase was detected. Our data demonstrate that the inhibition of EGFR-TK by gefitinib induces growth inhibition, apoptosis and cell-cycle arrest in NE gastrointestinal tumour cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for the treatment of NE tumour disease.

Antineoplastic Agents↗
PubMed2003

Ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in oesophageal cancer cells: involvement of the p38MAPK signalling pathway.

Specific ligands of the peripheral benzodiazepine receptor (PBR) are known to induce apoptosis and cell cycle arrest in oesophageal cancer cells. However, the underlying mechanisms are still unknown. Here, we investigated the transcriptional alterations and activation of protein kinases in response to PBR-specific ligands. Using cDNA arrays, we examined the transcriptional effects of the PBR-specific ligand FGIN-1-27 in two oesophageal cancer cell lines, KYSE-140 (squamous cell carcinoma) and OE-33 (adenocarcinoma). In oesophageal cancer cells, FGIN-1-27 induced extensive changes in the expression of genes involved in the regulation of apoptosis and cell cycle. Both in oesophageal cancer cell lines (KYSE-140, OE-33) we observed a strong upregulation of the growth arrest and DNA-damage-inducible genes, gadd45 and gadd153, in response to PBR ligands. gadd genes are known to be induced by p38MAPK activation. Using Western blotting we detected a time- and dose-dependent phosphorylation of p38MAPK, which was found to be functionally involved in gadd induction, apoptosis, and cell cycle arrest. In conclusion, our data indicate that PBR-specific ligands cause apoptosis and cell cycle arrest by activation of the p38MAPK pathway and induction of gadd45 and gadd153.

Apoptosis↗
PubMed2003

Oesophageal squamous cell neoplasia in head and neck cancer patients: upregulation of COX-2 during carcinogenesis.

Patients with (previous) head and neck cancer (HNC) are at high risk for developing second squamous cell cancer of the oesophagus. The role of cyclooxygenase-2 (COX-2) in oesophageal squamous carcinogenesis has not yet been investigated in this high-risk group. Therefore, this study examined COX-2 mRNA and protein expression in oesophageal biopsies and resected tissues of 44 HNC patients. The evaluation covered 55 oesophageal tissue samples (18 invasive oesophageal squamous cell cancers, four high- and eight low-grade dysplasias, 25 normal squamous epithelia) from the 44 patients. mRNA levels of COX-2 were measured by real-time PCR using a LightCycler. COX-2 protein expression was studied immunohistochemically and graded by a staining score. COX-2 mRNA was detected in all samples, and its levels correlated positively with the immunohistochemical staining score (P<0.05). COX-2 expression was upregulated during oesophageal squamous carcinogenesis in HNC patients, that is COX-2 expression increased significantly from normal oesophageal squamous epithelium to low- and high-grade dysplasia and finally to invasive squamous cell cancer (P<0.001). Our findings suggest that COX-2 upregulation contributes to oesophageal squamous carcinogenesis in HNC patients. Prospective studies are needed to evaluate the chemopreventive potential of COX-2 inhibitors in this high-risk group.

Base Sequence↗
PubMed2003

A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma.

BACKGROUND AND AIMS: This study assessed the efficacy and safety of irinotecan (CPT-11) in the treatment of patients with unresectable esophageal carcinoma. PATIENTS AND METHODS: Ten patients with esophageal squamous cell carcinoma (SCC) and three with adenocarcinoma (AC) were treated with CPT-11. Eight of the 13 patients were pretreated by surgery, radio-, or chemotherapy. CPT-11 was administered in repeated 6-week cycles consisting of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/m(2) given intravenously over 60 min; subsequent doses were adjusted based on tolerance and toxicity. Nine patients were evaluable for response. RESULTS: Two patients showed a partial response (one SCC, one AC) and two others disease stabilization (one SCC, one AC). The mean time to progression was 3.8 months. Mean survival since study entry was 6.1 months. In the 103 administrations we observed grade 3 or 4 toxicity on six occasions with diarrhea, five with neutropenia, and one with nausea and vomiting. Toxicity required dose reductions in five patients; in two of these patients treatment was stopped because of severe toxicity. No treatment related deaths occurred. CONCLUSION: CPT-11 as single-agent therapy is modestly effective against squamous cell cancer of the esophagus.

Aged↗
PubMed2003

Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma.

Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.

Adult↗
PubMed2003

A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication.

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication. We show here that a tumor-selective E1B-deleted RRCA can be tightly regulated by use of doxycycline (dox)-controlled adenoviral E1A gene expression, which in turn determines vector replication. RRCA replication is switched on by addition and switched off by withdrawal of dox. The system results in efficient tumor cell killing after induction by dox, whereas cells are unaffected by the uninduced system. It was also employed for efficient external control of transgene expression from cotransfected replication-deficient adenovectors. Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy. The concept of external control of RRCAs may help to improve the safety of cancer gene therapy.

Adenoviridae↗
PubMed2002

Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells.

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a new treatment modality for early esophageal neoplasia. With two absorption maxima in the visible light range (550 and 588 nm) hypericin is a very promising photosensitizer for PDT with incoherent light sources. We studied the effects of photosensitizing hypericin in both primary cell cultures and cell lines (squamous: Kyse-140 and adenocarcinoma: OE-33) of human esophageal cancer using an incoherent white light source. MATERIALS AND METHODS: Esophageal cancer cells were preincubated (4-24 h) with hypericin (10 nM-1 micro M) and then irradiated with a light energy dose of 30 J/cm(2). RESULTS: Hypericin showed strong phototoxic effects and induced apoptosis in a dose-dependent fashion. The IC(50) value of hypericin phototoxicity was approximately 30 nM in both squamous and adenocarcinoma cells. In the concentrations used nonphotoactivated hypericin showed no toxic or apoptotic potency. The phototoxicity of hypericin was compared to that of delta-aminolevulinic acid (5-ALA), which is already being used for photodynamic therapy of gastrointestinal cancer. 5-ALA produced similar phototoxic effects but at a much higher dose (IC(50) 182+/-8 micro M in Kyse-140 and 308+/-40 micro M in OE-33 cells). Moreover, 5-ALA did not induce apoptosis to a relevant extent. CONCLUSION: Hypericin is a very promising new photosensitizer for innovative photodynamic therapy of esophageal cancer. Both the well known clinical safety of hypericin and the lower costs of broad band light sources argue in favor of clinical trials.

Adenocarcinoma↗
PubMed2002

Expression of dopamine receptors and transporter in neuroendocrine gastrointestinal tumor cells.

C-11- or F-18-DOPA positron emission tomography (DOPA PET) is a new sensitive imaging technique for small neuroendocrine gastrointestinal tumors which evaluates the decarboxylase activity. To further characterize the dopaminergic system in neuroendocrine gastrointestinal tumor cells, we investigated the expression of both dopamine receptors and the transmembrane dopamine transporter (DAT) in the human neuroendocrine pancreatic cell line BON and in the neuroendocrine gut cell line STC-1. Both BON and STC-1 cells expressed mRNA of the dopamine receptors D2-D5 and DAT. mRNA of the dopamine receptor D1 was detected in BON cells only. Both in BON and STC-1 cells, expression of D2 and D5 receptors and DAT was also demonstrated immunocytochemically. For functional receptor characterization intracellular cAMP levels ([cAMP]i) were determined. Whereas in STC-1 cells dopamine and the D1-like (D1/D5) receptor agonist SKF 38393 increased [cAMP]i, [cAMP]i was decreased by dopamine or the D2-like (D2-D4) receptor agonist quinpirole in BON cells. Functional DAT activity was, however, not detected in either cell line. The presence of both dopamine receptors and of the DAT suggests an autocrine and/or paracrine function of dopamine in neuroendocrine gastrointestinal tumor cells. Yet neither the transmembrane dopamine transporter nor dopamine receptors are likely to contribute to positive DOPA PET imaging of neuroendocrine gastrointestinal tumors. However, these molecules may be of diagnostic importance when applying other dopaminergic system tracers.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

[Current epidemiology of carcinoma of the esophagus and cardia in Germany].

BACKGROUND AND OBJECTIVE: In the past 20-30 years the incidence of adenocarcinoma (AC) of the esophagus and the cardia has risen in western countries, while that of squamous cell carcinoma (SC) of the esophagus has largely stayed constant. Current data in the epidemiology of these cancers in Germany were analysed. METHODS AND MATERIAL: The data of the epidemiological cancer register of the Saarland (Old State of former West Germany) and the combined registers of the New States of Germany (former East Germany) and Berlin were collected. Because of the excellent registration procedures, data from the Saarland and the New States, Mecklenburg-Pommern, Brandenburg and Saxony were selected for this study. The incidence was calculated and corrected for age in relation to the world population. RESULTS: The incidence of esophageal AC among males in the Saarland rose from 0.22 per 100 000 population to 1.17 between 1986 to 1997, an increase of 432%, while in Brandenburg, Mecklenburg-Vorpommern and Saxomy it rose, between 1977 and 1998, from 0.23 to 0.8 i.e. by 248%. Esophageal SC incidence remained largely constant in both cancer registers since 1986. In 1998 it was 3.31 in the three New States of Germany and 5.05 in the Saarland. In females the incidence was markedly lower. In 1996-1998 fewer than 10% of cases of esophageal cancer were in UICC stage 1 (T 1 N 0 M 0, early carcinoma). Correspondingly the 5-year survival of all patients with esophageal carcinoma in the Saarland was less than 10% in 1971-1995. AC of the cardia also increased. In the three New States of Germany the incidence among males rose from 1.27 in 1977 to 2.18 in 1998, in females from 0.4 to 0.58. During the same period malignant tumors of the entire stomach, including the cardia, decreased in males from 29.5 to 17.1, in females from 14.3 to 9.2. CONCLUSION: In Germany, during the past 15-20 years, the incidence of esophageal AC and presumably also of AC of the cardia has increased. But the incidence of squamous cell carcinoma of the esophagus has remained largely constant. The proportion of early carcinoma and the 5-year survival with esophageal carcinoma remains under 10%.

Adenocarcinoma↗
PubMed2002

[Puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure].

UNLABELLED: Puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure. HISTORY: A 34-year old patient presented in reduced status with a sudden onset of fever, headache, backpain, abdominal pain, mild diarrhea, nausea with vomiting, and blurred vision. Within a few days an acute renal failure developed. INVESTIGATIONS: On admittance there was thrombocytopenia of 27/nl, CRP of 109 mg/l and proteinuria of 5 g/l, moderate glucosuria and erythrocyturia of 250/microliter. Renal biopsy showed acute hemorrhagic interstitial nephritis. DIAGNOSIS, THERAPY AND FOLLOW UP: Diagnosis of nephropathia epidemica was proven by puumala-virus IgM- and later IgG-antibodies. Hantaan-antibodies were negative. Maximum serum creatinine of 640 micromol/l and urea of 30.5 mmol/l developed on the 5(th) day after admission. Without specific therapy the patient recovered fast and there were no persisting abnormalities during a 2-year follow up. CONCLUSION: In young patients with acute renal failure of unknown origin with the above symptoms hantavirus-infection with the subtypes puumala and dobrava should be considered in Central Europe.

Acute Kidney Injury↗