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Biomedical subjects

Irene Sulzbacher

Publications and source records attributed to Irene Sulzbacher.

11 recordsLinked to original sources

Expression of c-kit in human osteosarcoma and its relevance as a prognostic marker.

AIMS: To examine the prognostic relevance of c-kit expression in human osteosarcomas and to evaluate the mutation status in exon 9 and exon 11 of the c-kit gene. METHODS: c-kit expression was examined in 100 human osteosarcomas by immunohistochemistry using paraffin embedded tumour tissues, and capillary sequencing of genomic DNA was performed to search for mutations in exons 9 and 11 of the c-kit gene. RESULTS: 20 osteosarcomas showed c-kit expression ranging from 5% to 90% (mean 5.9%; SD 16.74%). Furthermore, DNA sequences of exon 9 and exon 11 of the c-kit gene were not altered in these tumours. Overall and disease free survival analysis did not reveal any differences between patients with osteosarcoma with c-kit expression and those with c-kit negative tumours. CONCLUSIONS: C-kit expression is not a prognostic marker in patients with osteosarcoma. The protein expression is not linked to mutations in exon 9 or exon 11 of the c-kit gene. Therefore, these exons may not function as targets for treatment modalities based on the suppression of c-kit tyrosine kinase activity.

Adolescent↗

Tissue reactions induced by different embolising agents in cerebral arteriovenous malformations: a histopathological follow-up.

AIMS: Comparative histopathological analysis was performed in 47 incompletely embolised and resected cerebral arteriovenous malformations (AVMs). METHODS: Thirty-three AVMs were embolised with n-butyl-cyanoacrylate (NBCA), four with iso-butyl-cyanoacrylate (IBCA), seven with polyvinyl alcohol particles (PVA), one with a fibrin mixture, one with silicon pellets, and one with microcatheter balloons. Maximum exposure time (MET) of the embolising agent (interval between embolisation and surgery) ranged from <24 hours to 80 months. All AVMs were investigated regarding angionecrosis, angiofibrosis, acute inflammation, chronic inflammation, foreign-body reactions, vascular calcification, blood admixture to embolising cast, and capillary recanalisation within the AVMs. These parameters were correlated with MET, comparing different embolising agents, age, and sex. RESULTS: A typical sequence of events depending on MET is observed in all embolised AVMs: acute inflammation with mural angionecrosis is soon replaced by prominent chronic granulomatous vasculitis, which remains stable and is detectable for a very long time, even in AVMs with a MET of more than 6 years. CONCLUSION: Capillary recanalisation is always present in incompletely embolised AVMs, detectable after 3 months of MET, irrespective of the embolising agent used. Age and sex does not influence pattern and time course of tissue lesions and recanalisation in incompletely embolised AVMs.

Adolescent↗

CD9 expression is not a prognostic factor in human osteosarcoma.

CD 9, also known as Motility-Related Protein-1 (MRP-1), is a member of the transmembrane four superfamily and plays a crucial role in cell adhesion, motility and signalling events. Downregulation of CD 9 has been reported to be associated with tumour progression, metastasis and clinical outcome in various kinds of solid tumours. Although prognosis of osteosarcoma has been improved by chemotherapy during the last decades, the problem of non-responders remains. At the present time prognostic factors at diagnosis have not been clearly identified. Furthermore, there is a need for markers that predict the response to chemotherapy at the time of biopsy, allowing stratification of osteosarcoma patients. In this study we investigated the effect of CD9 expression on the response to chemotherapy and survival in osteosarcoma. The expression of CD9 was examined immunohistochemically in 52 patients with high grade osteosarcoma and the results were correlated with histologic response to chemotherapy, 5 year disease free and 5 year overall survival. In patients with osteosarcoma 22 of 52 cases (42%) were positive for CD 9 expression, the rest were negative. CD 9 expression status showed no statistically significant correlation with response to chemotherapy; 41% had a poor response and 59% a good response in the CD9 positive group. In the CD9 negative group 57% had a good and 47% had a bad response. No significant difference was found when comparing disease free survival (58.9% in CD9 positive- versus 69.3% in CD9 negative tumours; P = 0.99) and overall survival of patients (54.0% in CD9 positive- versus 58.1% in CD9 negative tumours; P = 0.90) with CD9 expressing tumours to those with reduced CD9 expression. In conclusion our findings suggest that in contrast to solid tumours, CD9 is unlikely to provide any additional prognostic information for clinical purposes in osteosarcoma patients.

Adult↗

Neoadjuvant radiochemotherapy of oral cavity and oropharyngeal cancer: evaluation of tumor response by CT differs from histopathologic response assessment in a significant fraction of patients.

BACKGROUND: Our aim was to compare and assess the predictive value of CT and histopathologic grading of tumor regression at primary tumor sites in patients with squamous cell carcinoma of the oral cavity and oropharynx after neoadjuvant (preoperative) radiochemotherapy (RCT). METHODS: We investigated 55 patients with carcinomas of the oral cavity and oropharynx who underwent RCT before curative surgery. Two blinded observers measured RCT-induced reduction of tumor volume in pretherapeutic and posttherapeutic CT scans. Volume changes were compared with histopathologic findings obtained at surgery. RESULTS: Histopathologic response evaluation revealed 31 complete remissions, 12 cases of partial response, and 12 nonresponders. We performed a logistic regression analysis to evaluate whether measured volume reduction could predict the likelihood of belonging to a certain response group. Taken together, we found 35 correct, 12 false-negative, and seven false-positive predictions. CONCLUSIONS: The extent of remission as assessed by CT scans 4 to 5 weeks after completion of neoadjuvant RCT leads to false predictions in a significant percentage of patients.

Adult↗

Investigation of apparent diffusion constant as an indicator of early degenerative disease in articular cartilage.

PURPOSE: To investigate the apparent diffusion constant (ADC) as a prospective magnetic resonance imaging (MRI) marker of early degeneration in articular cartilage. MATERIALS AND METHODS: Early degenerative changes were studied using in vitro MRI on cartilage-bone specimens excised from human femoral condyles. The loss of proteoglycans developed in vivo due to a degenerative process was compared with a gadolinium diethylenetriamine pentaacetate anion (Gd-DTPA(2-)) enhanced decrease of T(1) relaxation times, and with an increase of ADCs and T(2) relaxation times. RESULTS: Contrast enhanced T(1) values decreased and the diffusion constants increased in cartilage regions with depleted proteoglycans. The relative changes in diffusion constants were smaller than those of Gd-DTPA(2-) enhanced T(1), and in some proteoglycan-depleted regions no changes in the diffusion constants were detected. T(2) relaxation times showed considerable spatial variability that did not correlate with proteoglycan concentration. CONCLUSION: In contrast to Gd-DTPA(2-) enhanced T(1), which reflects changes in chemical composition, diffusion constants may reflect structural degradation of the cartilage matrix.

Cartilage, Articular↗

Expression of platelet-derived growth factor-AA is associated with tumor progression in osteosarcoma.

Platelet-derived growth factors are secreted by mesenchymal cells. The homodimer platelet-derived growth factor-AA especially stimulates bone cells through interaction with the platelet-derived growth factor-alpha receptor homodimer. In this study we wanted to determine the expression of the receptor and its ligand in human osteosarcomas and to correlate the expression of platelet-derived growth factor-AA and -alpha receptor with clinicopathological parameters. Fifty-seven osteosarcomas were immunohistochemically analyzed for expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor. Spearman's correlation coefficient revealed a strong correlation between the expression of platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor (r = 0.867). No differences were observed relative to gender, age, tumor stage, tumor location, and response to neoadjuvant chemotherapy between high or low platelet-derived growth factor-AA and platelet-derived growth factor-alpha receptor expression. High platelet-derived growth factor-AA expression correlated with tumor progression in univariate analysis (P = .0415; log-rank test), whereas platelet-derived growth factor-alpha receptor expression showed a trend toward a shorter disease-free survival, which failed to reach significance (P = .0627, log-rank test). In multivariate analysis, platelet-derived growth factor-AA expression remained a significant independent predictor of tumor progression (P = .021, Cox regression). Immunohistochemical analysis of platelet-derived growth factor-AA expression in osteosarcoma may be a useful marker of prognosis and may be considered as a possible target for novel therapeutic strategies.

Adolescent↗

Elective and emergent endovascular treatment of subclavian artery aneurysms and injuries.

PURPOSE: To demonstrate our short and long-term results after transbrachial treatment of subclavian artery aneurysms and injuries with stent-grafts in elective and emergency settings. METHODS: Ten of 12 consecutive patients (6 men; mean age 63.8 years, range 38-80) were treated electively with commercially prepared endografts delivered via a transbrachial access to repair a subclavian artery aneurysm (n=3) or an injury from a misplaced central venous catheter (n=7). Two patients required emergency treatment for a ruptured atherosclerotic aneurysm in one and an unintentional arterial puncture during placement of a central venous access in the other. Stent-graft patency during follow-up was assessed by physical examination with comparison of brachial blood pressures in all patients; computed tomography angiography (CTA) was performed in available patients. RESULTS: Successful deployment of stent-grafts with sealing of the lesion was achieved in all cases. There were 2 (17%) procedural complications. One patient developed an access-site hematoma that required surgical revision. The second patient, who had a right subclavian injury, suffered an embolic cerebral infarction. The primary stent-graft patency during follow-up (mean 11.6 months) was 100%. CTA examinations in 7 patients at a mean 18 months showed strut dislocation at the thoracic outlet without luminal narrowing in 1 patient. A 50% intraluminal narrowing due to compression between the clavicle and the first rib occurred in another patient. Six patients with a mean follow-up of 23 months (range 0.3-4.5 years) are still alive with patent stent-grafts. CONCLUSIONS: Endovascular stent-graft treatment of subclavian artery aneurysms and injuries is a less invasive alternative to surgical repair. Long-term results must still be confirmed in further studies.

Adult↗

Expression of platelet-derived growth factor-alpha alpha receptor is associated with tumor progression in clear cell renal cell carcinoma.

Platelet-derived growth factors (PDGFs) exert their biologic function by binding to 3 different tyrosine kinase receptor isoforms. Especially the PDGF-alpha alpha receptor binds PDGF proteins with high specificity, which results in growth stimulation. The expression of the receptor and its ligand was studied in human renal cell carcinomas (RCCs) by immunohistochemical analysis, and the expression of PDGF-alpha alpha receptor and PDGF-AA was correlated with clinicopathologic parameters of patients with clear cell RCC (CCRCC). In CCRCC, the mean expression of PDGF-alpha alpha receptor and PDGF-AA was 38.8% (range, 0.0%-96.0%) and 18.4% (range, 0.0%-90.0%), respectively. PDGF-alpha alpha receptor expression was significantly higher in grade 3 and grade 4 tumors compared with grade 1 and grade 2 tumors (P = .027; Mann-Whitney test), and high receptor expression correlated with tumor progression in univariate analysis (P = .0253; log-rank test), while PDGF-AA expression had no prognostic influence on the outcome of patients with CCRCC. Therefore, immunohistochemical detection of high PDGF-alpha alpha receptor expression in CCRCC is associated with adverse outcomes. Furthermore, the PDGF receptor-factor interaction loop may be considered as a possible target for novel therapeutic strategies.

Adult↗

Expression of osteopontin and vascular endothelial growth factor in benign and malignant bone tumors.

Osteopontin (OPN), one of the major non-collagenous proteins of bone matrix, is together with vascular endothelial growth factor (VEGF) a potent angiogenic protein. In this study we determined the expression of OPN in benign and malignant bone tumors and investigated the prognostic influence of OPN expression on the outcome of osteosarcoma patients. Fifty-seven osteosarcomas and 11 osteoblastomas as well as 5 bone specimens with remodeling sites were immunohistochemically analyzed for expression of OPN and VEGF. OPN was not detected in osteoblasts of remodeling sites. Osteoblastoma osteoblasts as well as osteoclastlike giant cells and osteosarcoma mononuclear cells showed variable staining. In osteosarcomas OPN and VEGF expression correlated with each other (r=0.390, P=0.003, Spearman's test). Although osteosarcoma patients with high VEGF expression showed a trend towards shorter overall survival ( P=0.0841, log-rank test), OPN expression had no influence on patients overall or on disease-free survival. Our data indicate that expression of this protein might be upregulated in bone neoplasia. Although OPN expression correlates with VEGF expression in osteosarcomas, OPN expression does not provide predictive information about the outcome of osteosarcoma patients.

Adolescent↗

High-resolution 3 T MR microscopy imaging of arterial walls.

PURPOSE: To achieve a high spatial resolution in MR imaging that allows for clear visualization of anatomy and even histology and documentation of plaque morphology in in vitro samples from patients with advanced atherosclerosis. A further objective of our study was to evaluate whether T2-weighted high-resolution MR imaging can provide accurate classification of atherosclerotic plaque according to a modified American Heart Association classification. METHODS: T2-weighted images of arteries were obtained in 13 in vitro specimens using a 3 T MR unit (Medspec 300 Avance/Bruker, Ettlingen, Germany) combined with a dedicated MR microscopy system. Measurement parameters were: T2-weighted sequences with TR 3.5 sec, TE 15-120 msec; field of view (FOV) 1.4 x 1.4; NEX 8; matrix 192; and slice thickness 600 microm. MR measurements were compared with corresponding histologic sections. RESULTS: We achieved excellent spatial and contrast resolution in all specimens. We found high agreement between MR images and histology with regard to the morphology and extent of intimal proliferations in all but 2 specimens. We could differentiate fibrous caps and calcifications from lipid plaque components based on differences in signal intensity in order to differentiate hard and soft atheromatous plaques. Hard plaques with predominantly intimal calcifications were found in 7 specimens, and soft plaques with a cholesterol/lipid content in 5 cases. In all specimens, hemorrhage or thrombus formation, and fibrotic and hyalinized tissue could be detected on both MR imaging and histopathology. CONCLUSION: High-resolution, high-field MR imaging of arterial walls demonstrates the morphologic features, volume, and extent of intimal proliferations with high spatial and contrast resolution in in vitro specimens and can differentiate hard and soft plaques.

Aged↗