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C Röcken

Publications and source records attributed to C Röcken.

At least 19 recordsLinked to original sources
PubMed2006

Impact of biomarkers on disease survival and progression in patients treated with octreotide for advanced hepatocellular carcinoma.

BACKGROUND: Current determination of prognosis for advanced hepatocellular carcinoma (HCC) is mainly based on clinical assessment. We aimed to determine the impact of biomarkers as predictive factors for HCC progression and survival during octreotide-based treatments. PATIENTS AND METHODS: We included patients who had been prospectively randomised to receive either octreotide (30 mg) alone monthly (n = 39) or in combination with rofecoxib (up to 50 mg bid daily, n = 32) for a minimum of 6 months, or until death occurred. RESULTS: Overall median survival (154 days) and median time to progression (94 days) were not different for both treatments and the biomarkers investigated (VEGF-A, IGF-1, PGE-2, ET-A) were similarly distributed amongst treatment groups. Combined univariate group analysis revealed that survival was decreased for an uptake ratio of > 2 on initial octreoscan (P = 0.05); baseline serum VEGF-A and IGF-1 were further significantly associated with survival. On multivariate analysis, uncorrected serum VEGF-A appeared to be the most significant predictor for tumor progression and survival. CONCLUSIONS: Biomarkers, in addition to established tumor markers, are independent predictors of tumor progression and survival in patients with advanced HCC treated with octreotide. Furthermore, the involvement of VEGF-A implies the inhibition of angiogenesis as a potential mechanism of action for this drug.

Aged↗
PubMed2006

[Interdisciplinary guidelines on diagnosis and treatment for extracerebral amyloidoses--published by the German Society of Amyloid Diseases (www.amyloid.de)].

Within the past 10 years, a new range of knowledge has been achieved in the field of amyloidosis, especially with regard to pathogenesis, diagnosis and therapy. Amyloidosis leads to variable and distinct symptoms and is caused by different underlying conditions. Some amyloidoses are acquired secondary to a chronic condition; others are caused by genetic mutations. Amyloid and amyloidosis occur more frequently than they are perceived. Among the frequent localized forms are the cerebral amyloidosis linked to Alzheimer disease (AD) and the pancreatic amyloidosis linked to diabetes mellitus. Among the most frequent systemic (extracerebral) forms is AL amyloidosis, which often has a poor prognosis and if untreated can rapidly lead to death. Systemic amyloidosis that happen at infancy are mainly AA amyloidosis that can progress to death already at early or at middle adulthood. Amyloidosis can be treated but therapeutic success significantly depends upon early diagnosis and proper classification of the amyloid type. It is mandatory that differential diagnosis demonstrate the presence of amyloid and clearly identify the type of the disease. Development of methods and techniques have contributed to improvements in the diagnosis and treatment. Early diagnosis and proper classification of amyloid is decisive for therapeutic options and upon them depend quality of life and mortality. The therapeutic spectrum is various and includes organ transplantation, chemotherapy, and anti-inflammatory strategies. Gene therapy and biological active substances have to be considered in the near future.

Amyloidosis↗
PubMed2006

Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis.

In cerebral amyloidoses, such as Alzheimer's disease, proteolytic processing of the precursor protein is a fundamental mechanism of the disease, since it generates the amyloid protein. However, the putative significance of proteases in extracerebral amyloidoses is less well defined. In this study, we investigated the biological significance of cathepsin (Cath) B, CathK, and CathL in the pathology and pathogenesis of extracerebral amyloidoses by using the murine model of reactive or secondary AA amyloidosis with three different cathepsin-deficient mouse strains. Extracerebral AA amyloid was induced by injecting amyloid-enhancing factor and silver nitrate into CathB(-/-), CathK(-/-), and CathL(-/-) mice. Wild-type mice served as a control. CathK(-/-) mice deposited over 90% more amyloid and CathL(-/-) mice 60% less amyloid than the control (p < 0.0001). The amyloid load in CathB(-/-) mice did not differ from that in wild-type mice. In vitro degradation experiments with recombinant human and murine serum amyloid A (SAA) 1.1 and CathK and CathL showed that CathL generates a large number of differently sized SAA cleavage products. One of these fragments spans the heparin/heparan sulphate binding site and the neutral cholesterol ester hydrolase activating region of SAA. CathK showed only endoproteolytic activity and did not generate any AA amyloid-like peptides. This study provides unequivocal evidence that proteases modulate amyloid load in extracerebral amyloidosis. CathL was identified as an amyloid-promoting and CathK as an amyloid-retarding cysteine protease. CathB may only modulate the primary structure of the amyloid peptide without affecting amyloid load.

Acute-Phase Reaction↗
PubMed2006

[Amyloid diagnostics in rheumatic diseases].

Amyloid is a pathological protein deposit in tissue which has a red eosin color when the slice preparation is stained with traditional hematoxylin and eosin and after Congo red staining under polarized light exhibits a characteristic apple-green polarization color. Over 26 different autologous physiological proteins have been described that can form amyloid. In surgical pathology, immunoglobulin light chain-associated AL amyloidosis is the most frequent generally occurring amyloidosis, followed by hereditary and nonhereditary ATTR amyloidosis and AA amyloidosis. AA amyloidosis mostly develops subsequent to chronic infectious or inflammatory underlying disease and can represent a potentially life threatening complication. The spectrum of causes for AA amyloidosis has changed in the past few decades and is now determined by chronic rheumatic diseases and hereditary periodic fever syndromes. Early diagnosis of an amyloidosis and its correct classification continue to pose a great challenge. Precise classification of the amyloid and amyloidosis is essential for prognosis assessment and treatment planning. In addition to anti-inflammatory management of AA amyloidosis, specific treatment strategies may possibly become available in the future.

Amyloidosis↗
PubMed2006

Diagnostic and therapeutic impact of double-balloon enteroscopy.

BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a new endoscopic method for examining the small intestine. Most reports of DBE have been from Japan, and very few data on this new technique have been reported by centers outside Japan. The aim of the present study was to determine the diagnostic yield of DBE, measure the frequency of management changes made on the basis of the results, and evaluate the clinical outcome for patients undergoing the procedure. PATIENTS AND METHODS: All patients undergoing DBE using a Fujinon enteroscope (length 200 cm, diameter 8 mm) during a 11-month period were studied. All of the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. They underwent small-bowel cleansing on the day before the procedure using a standard colon lavage solution. RESULTS: Seventy DBE procedures were carried out in 53 patients (34 men, 19 women; mean age 60 years, range 24 - 80) by the oral route in 46 cases and the anal route in 24. The indications for the examination were gastrointestinal bleeding (n = 29), suspected Crohn's disease (n = 6), abdominal pain (n = 4), polyp removal or evaluation in polyposis syndromes (n = 6), chronic diarrhea (n = 4), and surveillance or tumor search (n = 4). The mean duration of the procedure was 72 min (range 25 min - 3 h). The mean radiation exposure was 441 dGy/cm (range 70 - 1462), and the mean depth of small-bowel insertion was 150 cm (range 1 - 470 cm). It was possible to evaluate the entire small bowel in four patients (8 %). A new diagnosis was obtained in 26 of the 53 patients (49 %). The findings in the 70 procedures were angiodysplasia (n = 13), ulcerations or erosions (n = 5), jejunitis or ileitis (n = 5), tumors (n = 5), stenosis (n = 4), polyps (n = 5), lymphangiectasias (n = 4), Crohn's disease (n = 4), and normal (n = 17). DBE resulted in a therapeutic intervention (endoscopic, medical or surgical, excluding blood transfusions) in 57 % of the patients (30 of 53). The only complication (1.4 %) observed was one case of intraprocedural postpolypectomy bleeding, which resolved with injection of epinephrine. CONCLUSION: In almost two-thirds of the patients examined, DBE was clinically useful for obtaining a new diagnosis and starting new treatments, changing existing treatments, carrying out surgical intervention, or providing therapeutic endoscopy. DBE is a useful and safe method of obtaining tissue for diagnosis, providing hemostasis, and carrying out polypectomy.

Adult↗
PubMed2006

Ectopeptidases in tumour biology: a review.

Cell membrane-bound proteolytic enzymes (ectopeptidases) are integral membrane proteins, orientated asymmetrically with the catalytic site exposed to the extracellular surface, which enables a versatile range of physiological and pathological functions. Ectopeptidases may regulate the release of many growth factors and their receptors into the circulation, as well as activating or inactivating circulating signalling molecules, thereby regulating the availability of ligands for the corresponding receptors. Additionally, many of these ectopeptidases have functions not limited to proteolysis, but are able in themselves to function as receptors, transducing intracellular signals. A versatile range of functions, such as the modulation of cell-signalling, matrix degradation, cell adhesion and migration, which are particularly important for tumour cell growth and dissemination, are attributed largely to the ectopeptidases. Even a minor disruption in the normal proteolytic equilibrium can influence tumor progression, and a range of ectopeptidases, including neutral endopeptidase 24.11, aminopeptidase N, dipeptidyl peptidase IV, angiotensin-converting enzyme, and the disintegrin-metalloproteinases, have been shown to be involved in tumour development and metastasis. The ability to degrade and inactivate peptide hormones and growth factors, with the resultant modulation of the tumour-host interface, may play an important role in the pathogenesis, development or progression of a range of cancers, and the extracellular orientation of the ectopeptidases makes them particularly accessible, and therefore interesting, with regard to therapeutical applications.

Humans↗
PubMed2005

Proteolysis of serum amyloid A and AA amyloid proteins by cysteine proteases: cathepsin B generates AA amyloid proteins and cathepsin L may prevent their formation.

BACKGROUND: AA amyloidosis develops in patients with chronic inflammatory diseases. The AA amyloid proteins are proteolytic fragments obtained from serum amyloid A (SAA). Previous studies have provided evidence that endosomes or lysosomes might be involved in the processing of SAA, and contribute to the pathology of AA amyloidosis. OBJECTIVE: To investigate the anatomical distribution of cathepsin (Cath) B and CathL in AA amyloidosis and their ability to process SAA and AA amyloid proteins. METHODS: and results: CathB and CathL were found immunohistochemically in every patient with AA amyloidosis and displayed a spatial relationship with amyloid in all the cases studied. Both degraded SAA and AA amyloid proteins in vitro. With the help of mass spectrometry 27 fragments were identified after incubation of SAA with CathB, nine of which resembled AA amyloid proteins, and seven fragments after incubation with CathL. CathL did not generate AA amyloid-like peptides. When native human AA amyloid proteins were used as a substrate 26 fragments were identified after incubation with CathB and 18 after incubation with CathL. CONCLUSION: The two most abundant and ubiquitously expressed lysosomal proteases can cleave SAA and AA amyloid proteins. CathB generates nine AA amyloid-like proteins by its carboxypeptidase activity, whereas CathL may prevent the formation of AA amyloid proteins by endoproteolytic activity within the N-terminal region of SAA. This is particularly interesting, because AA amyloidosis is a systemic disease affecting many organs and tissue types, almost all of which express CathB and CathL.

Adult↗
PubMed2005

Expression of carbonic anhydrase 9 at the invasion front of gastric cancers.

BACKGROUND: Carbonic anhydrase IX (MN/Ca9) catalyses the reversible metabolism of carbon dioxide to carbonic acid and has also been linked to malignant transformation and hypoxia in various cancers. AIMS: To assess the expression and biological role of Ca9 in gastric cancer. METHODS: Using gastric cancer cell lines and tissues, we studied expression of Ca9 by western blot analysis, immunohistochemistry, and polymerase chain reaction. Biological changes after Ca9 transfection and after treatment with 5'-azadeoxycytidine were also analysed in cancer cell lines. RESULTS: Non-cancerous tissues strongly expressed Ca9 with membranous localisation. In contrast, Ca9 expression was frequently lost in gastric cancers (p<0.001). However, gastric cancers that retained Ca9 expression in cancer cells exhibited a shorter postoperative survival (p = 0.028). In vitro analysis revealed that loss of Ca9 expression in gastric cancer cell lines was restored after treatment with 5'-azadeoxycytidine and was associated with increased invasion (p<0.01). Moreover, AGS cells transfected with Ca9 exhibited significantly increased cell proliferation (p<0.05). CONCLUSIONS: A subgroup of gastric cancers retain Ca9 expression in cancer cells at the invasion front. While loss of Ca9 expression is regulated in part by methylation, re-expression of Ca9 is associated with increased invasion, supporting the hypothesis that increased Ca9 expression may contribute to invasion and thus advanced disease and tumour progression in a subset of gastric cancers.

Adult↗
PubMed2005

Canalicular immunostaining of aminopeptidase N (CD13) as a diagnostic marker for hepatocellular carcinoma.

BACKGROUND: Aminopeptidase N (CD13) is expressed in normal and neoplastic liver tissue, where it exhibits a characteristic canalicular pattern (CD13(can)), similar to that seen for CD10 and when antibodies crossreact with biliary glycoprotein I (p-CEA). AIM: To compare the putative diagnostic use of CD13(can) in differentiating between hepatocellular (HCC) and non-hepatocellular carcinomas metastatic to the liver (non-HCC). METHODS: A retrospective study comparing 53 HCC specimens with 32 non-HCC specimens. Immunostaining was performed with HepPar1 and antibodies directed against CD10, CD13, p-CEA, and alpha fetoprotein (AFP). RESULTS: In the HCC group, a canalicular staining pattern was found for CD13, p-CEA, and CD10 in 51, 43, and 33 specimens, respectively. HepPar1 was positive in 29 and AFP in 17 HCC specimens. In the non-HCC group, canalicular immunostaining for CD10 and p-CEA was confined to non-neoplastic liver tissue. One poorly differentiated cholangiocarcinoma showed apical expression of CD13, resembling to some extent CD13(can). Sensitivity and specificity were 96.2% and 97.0%, respectively, for CD13(can), 81.1% and 100% for p-CEA(can), 62.3% and 100%, for CD10(can), 54.7% and 99.9% for HepPar1, and 32.1% and 100% for AFP. CONCLUSIONS: These results show that CD13(can) is more sensitive in differentiating between HCC and non-HCC than CD10(can), p-CEA(can), HepPar1, and AFP.

Aged↗
PubMed2004

[Visualization of a solitary myeloma of the sternum by ultrasonography].

We report on a 32-year-old patient with a 9 month history of pain of the mid-third of his sternum. The laboratory results as well as other diagnostical methods (MRI and bone scintigraphy) were negative. The ultrasound examination revealed an interruption of the corticalis reflex beneath the sternal synchondrosis of a length of 4 cm. Under suspicion of an osteolysis we performed an open biopsy. The histological analysis made the diagnosis of a solitary myeloma. Therefore ultrasonography is able to depict tumerous infiltrations of the sternum if the anterior corticalis is involved and allows therapeutical consequences.

Adult↗
PubMed2003

Dual role of serum soluble E-cadherin as a biological marker of metastatic development in gastric cancer.

BACKGROUND: Soluble E-cadherin serum levels as a potential biological marker for gastric cancer were analysed with special consideration to clinical and pathological features. METHODS: Seventy-one healthy control subjects and 166 patients with gastric cancer were enrolled. Gastric cancer patients were classified into intestinal-type (51%) and diffuse-type (49%), according to Laurén. Soluble E-cadherin serum levels were measured with enzyme-linked immunosorbent assay. RESULTS: The mean logarithmic concentrations of soluble E-cadherin in gastric cancer patients were significantly higher than those of control subjects, with an average of 4.03 (+/- 0.32) versus 3.86 (+/- 0.24), respectively (P < 0.0001). The concentration of soluble E-cadherin was significantly higher in the intestinal-type group than in the diffuse-type group, with an average of 4.07 +/- 0.3 versus 3.98 +/- 0.34, respectively (P = 0.0494). In the intestinal-type group, concentrations of soluble E-cadherin were significantly higher in more advanced stages (stages III-IV) than in earlier stages (stages I-II), with an average of 4.13 +/- 0.29 versus 3.96 +/- 0.31, respectively (P = 0.0234). In the diffuse-type group, concentrations of soluble E-cadherin were significantly higher in localized than in metastatic gastric cancer, with an average soluble E-cadherin concentation of 4.15 +/- 0.3 versus 3.95 +/- 0.32, respectively (P = 0.0139). CONCLUSION: Serum soluble E-cadherin concentrations exhibit a completely different pattern in intestinal-type and diffuse-typegastric cancer. Serum levels are increased in intestinal-type gastric cancer, especially in advanced stages, whereas in diffuse-type gastric cancer E-cadherin levels are decreased in advanced, metastasized cancer.We conclude that soluble E-cadherin concentrations should be interpreted along with Laurén classification and thus might serve as a biological marker in intestinal-type gastric cancer.

Adolescent↗
PubMed2002

Expression of cathepsins B, H, K, L, and S during human fetal lung development.

Cathepsins are involved in lysosomal protein degradation, proenzyme activation, antigen processing, and hormone maturation. They are secreted by tumor cells and macrophages and catalyze the remodeling of extracellular matrix proteins. To gain insight into the expression pattern of cathepsins during fetal lung development, the expression of cathepsins B, H, K, L, and S at protein and mRNA levels were evaluated by using immunohistochemistry and in situ hybridization. Early expression of cathepsins B, H, and K was found in epithelial cells of the branching presumptive bronchi (<12th week of gestation). The most intense cathepsin K-specific immunoreactivity was found in developing airways with a lumen. Cathepsin K was found in epithelial cells only, whereas in contrast, cathepsins B and H were detected both in epithelial and interstitial cells. During fetal maturation, interstitial cells displayed cathepsin L immunoreactivity and, in the saccular phase (>26th week of gestation), both cathepsin L and S immunoreactivities. A continuous decline in the proportion of cathepsin H-positive interstitial CD68-positive cells was observed. These discrete temporal and spatial variations in cathepsin expression during organogenesis of the human lung indicate different physiological roles for the individual enzymes in different cell types and developmental stages.

Antigens, CD↗
PubMed2002

[Differential diagnosis of amyloidosis].

Amyloid is defined as a proteinaceous tissue deposit that shows a typical green birefringence in polarized light after staining with Congo red, the presence of non-branching linear fibrils of indefinite length with an approximate diameter of 10-12 nm, and a distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril. Amyloid may deposit locally, organ-limited, tumor-like, or may present as a generalized disease. The origin of amyloid is diverse: twenty different fibril proteins have been described so far. The precursor proteins differ from each other in their primary structures and functions. The only common denominator is the propensity to form anti-parallel cross beta-fibrils under certain circumstances. Early diagnosis of amyloid is still a major challenge in surgical pathology. Histological proof can be obtained using Congo red staining and polarisation microscopy. However, small deposits may be difficult to discern and sensitivity can be improved by using fluorescence microscopy. Classification of amyloid is mandatory, since amyloid is treatable and different treatment regimens are applied to different amyloid diseases. AA amyloidosis requires intensified treatment of the underlying disease. Patients with generalized AL amyloidosis receive high dose chemotherapy and stem cell transplantation. Familial amyloidoses (AApoAI, AFib, ATTR) may undergo liver transplantation.

Amyloidosis↗
PubMed2001

Cathepsin K--a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical site. Its enzymatic characteristics, particularly its high matrix-degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific proteolytic capability.

Adult↗
PubMed2001

[Hepatobiliary cystadenoma].

INTRODUCTION: Hepato-biliary cystadenomas are rare intrahepatic cystic tumours. The correct preoperative diagnosis of this lesion is difficult. METHODS: We report four cases of hepato-biliary cystadenoma treated in our department from January 1995 to December 1999. RESULTS: The symptoms were unspecific. Preoperative computed tomography showed signs of an echinococcal cystic lesion in two patients, but there were no antibodies against an echinoccocal species in the serum. We performed a complete resection of the cystic tumour in three patients and a subtotal resection of a hepato-biliary cystadenoma in one, because of involvement of the hepatic portal structures. We did not find a malignant transformation to a hepato-biliary cystadenocarcinoma. CONCLUSION: Complete excision of a cystadenoma with a wide margin of normal liver tissue is the treatment of choice, because several reports have described malignant transformation of this kind of tumour. Taking a rapidly frozen section during the operation is an important step in the treatment of cystic liver lesions. A cystic liver lesion with several walls and a elevated CA 19-9 can predict a mucinous cystadenoma or cystadenocarcinoma.

Adult↗