PubMed Health⌕ Search

Biomedical subjects

S Krüger

Publications and source records attributed to S Krüger.

At least 19 recordsLinked to original sources
PubMed2007

Prognostic significance of clusterin immunoreactivity in breast cancer.

Clusterin (CLU) is involved in a variety of biological processes and has been found to be expressed even in many human malignancies, including breast cancer. Currently, there are only few data on the prognostic value of CLU in breast cancer. We therefore evaluated the relationship between CLU expression and clinicopathological parameters as well as relapse-free survival (RFS) and metastasis-free survival (MFS) of 141 breast cancer patients using the monoclonal antibody 7D1. CLU expression was found in 26% of cases and correlated significantly with high histological tumor grade and high Ki-67 labeling index (p=0.026 and p=0.010, respectively). Univariate Cox regression analysis revealed that CLU expression was tendentiously associated with RFS (p=0.068; relative risk [RR]: 1.77) and MFS (p=0.122; RR: 1.57). In a multivariate analysis, tumor grade, stage, estrogen receptor status and patients age (concerning RFS) as well as grade and lymph node status (concerning MFS) were identified as significant independent prognosticators. CLU expression showed an independent prognostic relevance concerning prediction of RFS by trend (p=0.110; RR: 1.81). We conclude from our data that estimation of CLU immunoreactivity may be helpful as a supplementary criterion to better assess the tumors propensity to relapse in selected cases of breast carcinoma.

Adult↗
PubMed2006

[Mixed episodes in bipolar disorder: a review].

Affective mixed states in bipolar disorders are a current matter of scientific debate and represent a complex clinical picture with coexisting manic and depressive symptoms. Treatment of mixed states is regarded as an important challenge. As diagnostic uncertainties complicate systematic clinical evaluations of this patient group, generally accepted clinical treatment guidelines are lacking yet. In this review the significance as well as the problems and risks of new treatment options are discussed.

Anticonvulsants↗
PubMed2006

[Odontogenic tumors in childhood - case report and review of literature].

BACKGROUND: Odontogenic tumors are a heterogenic group of neoplasias of the oral cavity, whose biological behaviour reaches from true hamartomas to highly malignant tumors. PATIENT: We describe the case of a 4 year old caucasian girl presenting with eruption disturbance of a primary tooth and corresponding maxillary tumor. After surgical removal of the mass, histological examination classified the tumor as ameloblastic fibroodontoma. This very rare neoplasm is of odontogenic origin. DISCUSSION: Following our case report, the variety of odontogenic tumors regarding tumor biology, clinical symptoms and therapeutic options in childhood are discussed. CONCLUSION: In case of complaints or clinical symptoms paediatricians should take the possibility of such neoplasias into consideration.

Alveolar Process↗
PubMed2006

[Bone formation in the ureter. Osseous metaplasia of an obstructed ureter].

Bone formation outside the skeleton is well known. Yet, ossification within the urogenital tract is rare. The case of a patient with distal ureteral obstruction, hydronephrosis, and subsequent circular osseous metaplasia of the ureter is presented. Open transperitoneal right-sided nephrectomy with partial resection of the ureter was performed. Intraoperatively and in histopathologic examination circular bone formation adjacent to the ureteral wall was detected. There was no evidence of malignancy. Early animal experiments in the twentieth century showed that bone metaplasia may be induced by epithelium of the urinary tract under certain conditions such as ischemia, inflammation, necrosis, sclerosis, and trauma. Osseous metaplasia may therefore be considered a differential diagnosis of calcification of the upper urinary tract in the absence of urolithiasis.

Aged↗
PubMed2006

Localized nodular pigmented villonodular synovitis of the upper ankle joint--diagnosis and treatment.

This paper introduces a case of local pigmented villonodular synovits (PVNS) of the upper ankle joint in a 37-year old patient. PVNS is a neoplasia of the synovial membrane. Two different entities of PVNS are known: generalized diffuse and local nodular. They differ in their degree of destruction and growth configuration, which is crucial for prognosis and operative treatment. The most common location of the local nodular form is the knee joint, followed by the finger joints. Occurrence in the ankle joint is not common but should be considered if clinical findings are present. MRI is the method of choice for diagnosis and assessment of the bone situation. Treatment consists of radical excision of the neoplasia. Radiosynoviorthesis is recommended as a post-operative treatment to increase the probability of a total removal of persisting PVNS cells. The rate of recurrence seems to be between 8 and 46%.

Adult↗
PubMed2006

Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours.

BACKGROUND: Integrated positron emission tomography (PET)/computed tomography (CT) scanners have been recently introduced in the diagnostic work-up of suspected pulmonary malignancy and demonstrate encouraging results in the staging of nonsmall-cell lung cancer. OBJECTIVE: To evaluate the usefulness of integrated FDG PET/CT in pulmonary carcinoid tumours. SETTING: University hospital. METHODS: We studied 13 patients (mean age +/- 1 SD, 57 +/- 11 years) with pulmonary carcinoid tumours. All patients demonstrated a single pulmonary lesion. Integrated PET/CT scan and surgical resection were performed in all patients. RESULTS: The pulmonary lesion size ranged from 1.1 to 5.0 cm. Final histological diagnosis confirmed 12 typical and one atypical pulmonary carcinoid. Mean proliferation rate of the typical carcinoids was 1.7 +/- 1.4%. None of the patients had recurrent carcinoid disease or died during follow-up (864 +/- 218 days). Mean standardized uptake value (SUV) of (18)F-fluorodeoxyglucose (FDG) in typical carcinoids was 3.0 +/- 1.5 (range 1.2 - 6.6); SUV in the atypical carcinoid was remarkably high with a value of 8.5. The SUV was lower than 2.5 in 6 of 12 patients (50%). Mediastinal lymph node metastases or extrathoracic metastases were not detected in any patient. CONCLUSIONS: (18)F-fluorodeoxyglucose PET/CT imaging improves accurate localization of metabolic activity and thus the interpretation of pulmonary lesions on CT. FDG uptake in pulmonary carcinoid tumours is often lower than expected for malignant tumours. Therefore, surgical resection or biopsy of lesions suspected to be carcinoids should be mandatory, even if they show no hypermetabolism on FDG PET images.

Adult↗
PubMed2006

Respiratory motion compensation with tracked internal and external sensors during CT-guided procedures.

This paper investigates the possibility of using the motion of a patient's anterior surface in combination with a motion model to compensate for internal respiratory motion during tracked biopsies. Position data from two electromagnetically tracked sensors, one placed on the patient's sternum, the other incorporated into a biopsy needle, were acquired during a liver biopsy. The data were used to evaluate the correlation between the position measurements of the two sensors and to derive an affine motion model to assess respiratory motion compensation for image-guided interventional procedures. The correlation reached up to 94% for ranges of steady respiration. The residual motion of the internal sensor after compensation is reduced by a factor of approximately four.

Biopsy↗
PubMed2006

Multi-organ affecting CMV-associated cryoglobulinemic vasculitis.

We report on a 67-year-old female patient who was admitted to our intensive care unit with acute renal failure and severe hypoxemia. Transiently, the patient had to be treated with kidney replacement therapies and artificial ventilation. The actual illness started with general weakness, recurrent bloody diarrhea and intermittent dermatitis of the lower legs. Skin symptoms were initially observed 2 years before the actual clinical findings. The bloody diarrhea was attributed to an inflammatory stenosis of the sigma. The life-threatening clinical aggravation was due to diffuse alveolar hemorrhage and alveolitis. In the search for the cause of the systemic disease, both a monoclonal y-globulinemia, causing a cryoglobulinemia type II and an acute cytomegalovirus infection were diagnosed. Additionally, the course of the disease was complicated by a secondary antibody deficiency as well as an endocarditis of the aortic valve caused by Enterococcus faecium. A cryoglobulinemic vasculitis type II was histologically found in biopsy specimen of the kidney. Thus, the present case reports on a coincidence of a monoclonal gammopathy causing a cryoglobulinemia type II with extensive organ involvement and a florid CMV infection. We hypothesize that the CMV infection has triggered the cryoglobulinemia and its particular severe organ involvement.

Aged↗
PubMed2005

Effects of the angiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis.

BACKGROUND: As angiogenesis is one of the key steps in tumor growth, invasion, and metastasis, antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. We investigated the cytotoxic, anti-adhesive, and anti-invasive effects of angiostatin in vitro and on intraperitoneal tumor growth in a laparoscopic rat model of peritoneal carcinomatosis using CC531 colon adenocarcinoma cells. METHODS: The in vitro adhesion and cytotoxicity assays were performed with microtiter plates, and the invasion assay with Transwell dual chambers. Normal saline was used as control. In in vivo experiments, CC531 adenocarcinoma cells were intraperitoneally given to Wistar Albino Glaxo rats after the establishment of a pneumoperitoneum. The animals received angiostatin in different doses intraperitoneally, and in some, angiostatin was additionally administered subcutaneously. Saline was used as control. After 21 days, the animals were euthanized to determine the intra-abdominal tumor weight. RESULTS: In in vitro experiments, there was no effect of angiostatin on the viability of tumor cells in the cytotoxicity assay, but there was a significant inhibition of tumor cell adhesion and invasion (p<0.05 and p<0.01) in all angiostatin concentrations. In in vivo experiments, an intraperitoneal application of 20 microg angiostatin, but not 10 microg, significantly (p<0.005) decreased the intraperitoneal tumor weight compared with controls. This effect was most pronounced after the combined intraperitoneal and subcutaneous applications. CONCLUSION: Angiostatin given intraperitoneally at a dose of 20 microg alone or in combination with subcutaneous application significantly diminishes intraperitoneal tumor growth in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic surgery for colorectal cancer.

Adenocarcinoma↗
PubMed2005

Inhibition of bcl-2 enhances the efficacy of chemotherapy in renal cell carcinoma.

OBJECTIVES: Renal cell cancer (RCC) is highly resistant to chemotherapy. Increased expression of the antiapoptotic gene bcl-2 in tumors is known to be associated with poor responses to systemic treatment of cancer. Down-regulation of bcl-2 expression using antisense oligonucleotides (asON) has been shown to increase chemosensitivity in clinical phase I-III studies with various cancers. However, no studies on the efficacy of this approach in RCC have been reported so far. This study aimed to evaluate whether bcl-2 asON could enhance efficacy of chemotherapy in human RCC. MATERIAL AND METHODS: Expression of bcl-2 mRNA and protein was analyzed in different RCC cell lines by RT-PCR and Western blot. Cells with high or low bcl-2 mRNA and protein expression were treated with different concentrations of bcl-2 asON in combination with cisplatin. AsON-induced down-regulation of bcl-2 mRNA and protein was documented by RT-PCR and Western blot. Treatment effects on cell viability were analyzed by colorimetric tetrazolium (MTT) assay. Immunohistochemical staining of M30-positive cells was performed for quantification of apoptotic cells. RESULTS: Transfection of high bcl-2 expressing cells with bcl-2 asON alone induced no reduction of cell viability at a concentration range from 100-1000 nM. In combination therapy, pretreatment with asON significantly enhanced MTT reduction after cisplatin treatment. IC50 concentrations of cisplatin were 1 microg/ml with and 2.7 microg/ml without prior incubation. The marked reduction of cell viability correlated with an 8-fold increase of apoptotic cells after combination treatment. Only a minor increase of cisplatin effectivity was noted after asON preincubation of cells with lower bcl-2 expression. CONCLUSIONS: The combination of cisplatin and bcl-2 antisense ON exerts significantly greater effects on cell viability and apoptosis than either agent used alone on human RCC cells. These data indicate that inhibition of bcl-2 expression may be an attractive therapeutic strategy in RCC tumors with high bcl-2 expression.

Antineoplastic Agents↗
PubMed2005

[Combination treatment with antisense oligonucleotides and chemotherapy in vitro].

Oncological therapy strategies are increasingly concentrating on the causal, molecular changes involved in carcinogenesis. So called "smart drugs" such as antisense oligoneucleotide (AsON) can be used as specific inhibitors of individual genes. AsONs have shown their effectiveness in many studies. Clinical studies have demonstrated, however, that for many tumours the inhibition of a single gene is, due to multigenetic alteration, largely ineffective. The combination of AsONs with conventional chemotherapeutic agents is currently being investigated in phase III studies. In these studies, chemotherapeutic agents have been evaluated in cell culture together with AsON against the proliferation associated Ki-67 gene, as well as against the apoptosis associated bcl-2 gene via RT-PCR, immunochemistry and MTT cell viability assay. For both AsONs, significant target inhibition was achieved in cell culture with a high target gene expression. The prior treatment of tumour cells with bcl-2 AsON significantly increased the effectiveness of chemotherapy, while the combination of conventional chemotherapeutic agents with Ki-67 AsON showed no synergistic effects.

Animals↗
PubMed2005

Relationship between donor factors, immunogenic up-regulation, and outcome after kidney transplantation.

Epidemiological data show that the cause of brain death as well as the condition of the organ donor have considerable influence on the outcome of kidney transplantation. An early immunogenic up-regulation, which already exists at the time of organ removal seems to be primarily responsible. So far it has remained unclear which donor factors cause this effect. In a prospective study of 37 organ donors a 0-hour biopsy was performed at the time of explantation to measure the expression of HLA-DR and endothelin-1 (ET-1) immunohistologically using the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. The transplant outcome and the immunohistological results were correlated with various donor factors. Statistically significant correlations were seen with the following parameters: the donor serum creatinine prior to explantation correlated with the incidence of delayed graft function (DGF: 104 +/- 39 vs 78 +/- 35 micromol/L versus no DGF n = 37; P = .043). Early graft loss after transplantation correlated significantly with increased numbers of leukocytes as well as with decreased O2 saturation in the donor immediately before explantation (leucocytes: 16.7 +/- 6.8 vs 12.6 +/- 4.6/nL, n = 37; P = .036; O2 saturation: 94.1% +/- 6.9%, vs 97.7% +/- 2.3%, n = 37; P = .026). Further, donor-independent factors that correlated with acute rejections included cold ischemic time (P = .031), HLA mismatches (P = .028), and occurrence of DGF (P = .033). The degree of HLA-DR expression (range 0 to 2) correlated significantly with early graft loss (2.0 +/- 0.2 vs 1.33 +/- 0.9 for graft function, n = 37; P = .01) as well as the ET-1 expression with DGF (2.0 +/- 0.3 vs 1.5 +/- 0.7 versus no DGF, n = 37; P = .016). In summary, marginal donors should be seen as high immunological risk situations that need careful conditioning.

Biopsy↗
PubMed2005

[Ki-67 antisense therapy in murine renal cell carcinoma models].

PURPOSE: The Ki-67 antigen is only expressed in proliferating cells. Previously, it was shown that Ki-67 derived antisense oligonucleotides (asONs) specifically inhibit the proliferation of tumor cells and tumour growth in vitro and in subcutaneous bladder and prostate tumor models. We intended to evaluate the effects of this therapeutic concept in two renal cell carcinoma (RCC) models. MATERIAL AND METHODS: Human RCC cells (SK-RC 35) were initially transfected with FITC-labeled ONs and diffferent cationic lipids to analyze the transfection efficacy by flow cytometry (FACS). The potency of 14 different ONs sequences was compared by quantitative RT-PCR in vitro. For in vivo testing, ONs were administered to immunocompetent Balb/c mice bearing orthotopic RENCA tumors as well as to SCID mice bearing subcutaneous RCC SK-RC 35 xenografts. Tumor sizes and final tumor weights were documented. Additionally, several immunohistochemical staining procedures were performed. RESULTS: FACS analysis showed highly effective transfection conditions in vitro. Systemic administration of asONs significantly decreased the tumour growth in the RENCA model (p < 0.05) and in the SCID mouse model (p = 0.009). Immunohistochemical staining of tumor specimens revealed a marked down-regulation of target protein and a slight increase in apoptotic cells after antisense treatment while the microvessel count was not significantly altered. CONCLUSION: These results demonstrate that the Ki-67 antigen represents a suitable antiproliferative target and that asONs directed against this target are potent drugs that induce a significant inhibition of renal tumor growth in different mouse models.

Animals↗
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↗