Biomedical subjects

Christian Hafner

Publications and source records attributed to Christian Hafner.

26 records · Page 2Linked to original sources

PubMed2004

Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting.

Gene expression profiling by cDNA array analysis in melanoma is hampered by the need for large amounts of RNA to prepare reliable probes for array hybridization. On the other hand, for ex vivo analysis of malignant cells from melanocytic tumors laser pressure catapulting is an essential prerequisite to obtain noncontaminated melanocytic preparations; however, laser pressure catapulting prepared material provides only nanogram amounts of RNA. In this study we present an approach to overcome these limitations by combining laser pressure catapulting and real-time polymerase chain reaction based SMART cDNA amplification technology. Reproducible and reliable hybridization patterns from about 500 laser pressure catapulting prepared cell equivalents from 22 cases of melanocytic tumors were generated using array analysis. Univariate analysis revealed significant differences of the expression pattern of melanocytic nevi, melanomas, and melanoma metastases. Multivariate analysis with four genes being the best univariate discriminative features (tyrosinase related protein 2, translation initiation factor 2 gamma, ubiquitine conjugating enzyme E2I and one expressed sequence tag) allowed clustering of nevi, melanomas, and melanoma metastases with an accuracy of 82%. Data validation was performed by additional quantitative reverse transcription-polymerase chain reaction (TaqMan-reverse transcription-polymerase chain reaction). Taken together, this study shows, that (1) array analysis is feasible on tumors with rather low cell numbers, and (2) differences in expression profiles allow discrimination between benign and malignant lesions. Expression patterns of marker genes defined in unequivocal histopathologic entities may improve the diagnostic and prognostic assessment of difficult melanocytic lesions, which is still the hardest problem in dermatopathology.

Biopsy↗

PubMed2004

Optimization of photonic crystal structures.

We report on the numerical structural optimization of two-dimensional photonic crystal (PhC) power dividers by using two different classes of optimization algorithms, namely, a modified truncated Newton (TN) gradient search as deterministic local optimization scheme and an evolutionary optimization representing the probabilistic global search strategies. Because of the severe accuracy requirements during optimization, the proper PhC device has been simulated by using the multiple-multipole program that is contained in the MaX-1 software package. With both optimizer classes, we found reliable and promising solutions that provide vanishing power reflection and perfect power balance at any specified frequency within the photonic bandgap. This outcome is astonishing in light of the discrete nature inherent in the underlying PhC structure, especially when the optimizer is allowed to intervene only within a very small volume of the device. Even under such limiting constraints structural optimization is not only feasible but has proven to be highly successful.

Journal Article↗

PubMed2003

Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors.

BACKGROUND: Systemic therapy options for patients with advanced angiosarcomas are limited, and their prognosis is poor. The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients. Therefore, in a pilot study, the efficacy of metronomically scheduled, low-dose trofosfamide in combination with the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, and the selective cyclooxygenase-2 inhibitor, rofecoxib, was evaluated in patients with advanced vascular malignancies. METHODS: Six patients with advanced and pretreated but progressive, malignant vascular tumors (5 angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days, trofosfamide (3 x 50 mg per day orally). The therapy was administered continuously until progression was observed. If necessary, doses were modified according to side effects. RESULTS: Two patients responded with complete remission of disease, one patient responded with partial remission, and three patients achieved stabilization of disease (no change). The median progression-free survival was 7.7 months (range, 2-15 months). Side effects generally were mild (World Health Organization Grade 1-2). Hospitalization was not necessary. CONCLUSIONS: This new triple combination of low-dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors.

Administration, Oral↗

PubMed2003

Molecular genetic analysis excludes implantation metastasis of basal cell carcinomas.

Basal cell carcinoma (BCC) of the skin is the most common tumor in the white population. A 66-year-old man developed 2 BCCs at the left parietal region of the head and at the helix of the left ear. The 2 lesions matched exactly when pressing the ear against the head, suggesting an implantation metastasis mechanism. Molecular genetic techniques were used to confirm or exclude such a mechanism in this rare clinical constellation. Tumor tissues were precisely microdissected for DNA isolation. Exons 5-9 of the p53 tumor suppressor gene were directly sequenced. In addition, loss of heterozygosity analysis of chromosome 9q was performed using 5 polymorphic microsatellite markers. The BCC of the ear revealed a p53 mutation at codon 273, whereas the other one lacked this mutation. In addition, the smaller BCC of the ear showed loss of heterozygosity at 9q33.3, in contrast with the larger BCC. Interestingly, histologically normal skin of the ear distant from the small BCC had the same deletion, indicating a field defect of this skin patch at 9q33.3. Molecular genetic analysis clearly demonstrated different genetic alterations of the two BCCs and therefore most likely excludes a mechanism of implantation metastasis.

Aged↗

PubMed2003

Loss of EphB6 expression in metastatic melanoma.

Overexpression of various members of the Eph receptor tyrosine kinases and their ephrin ligands has been frequently reported in cancer. In contrast, a loss of EphB6 gene expression has been correlated with a poor prognosis in human neuroblastoma, suggesting a distinct role for this receptor compared to other family members. More recently, an important role of EphB6 signalling in T-cells has been described, suggesting possibly deleterious immunologic effects of a loss of EphB6 in cancer progression. We investigated the expression of EphB6 in melanocytic tumors. EphB6 mRNA of 22 microdissected tissues (7 benign nevi, 7 melanomas, 8 metastases) and 10 different cell lines (normal melanocytes, non-metastatic/metastatic melanoma cell lines) were measured by quantitative real-time RT-PCR. For visualization of EphB6 protein expression, immunohistochemistry of 32 melanocytic lesions were performed. On the mRNA level, the benign nevi revealed the highest EphB6 expression (mean = 1.43), while melanomas (mean = 0.63) and metastases (mean = 0.08; p=0.001) displayed a progressive and significant reduction of EphB6 expression. Accordingly, established melanoma cell lines with metastatic potential showed low EphB6 expression in comparison to normal melanocytes and to most of the melanoma cell lines. Immunohistochemistry revealed homogeneous staining in common nevi, whereas in malignant melanomas and metastases a heterogeneously positive to completely negative EphB6 staining was observed. Remarkably, Spitz nevi stained similarly to ordinary melanocytic nevi. Taken together, we show that melanoma progression to metastatic disease is associated with a significant reduction of EphB6 gene expression which may have considerable consequences for the prognosis of malignant melanoma patients and possible gene-therapeutic approaches.

Adolescent↗

PubMed2002

Modeling of discontinuities in photonic crystal waveguides with the multiple multipole method.

A method for the simulation of discontinuities in photonic crystal defect waveguides is presented. This frequency domain technique is based on the multiple multipole method. In contrast with other known techniques, spurious reflections (due to the impedance mismatch at the waveguide terminations) are avoided. The absence of spurious reflections allows one to characterize precisely the intrinsic behavior of the sole discontinuity, reducing at the same time the size of the simulation domain. To achieve a perfect impedance matching, the guided modes of infinitely long waveguides corresponding to the input and output channels of the discontinuity are first computed using a supercell approach. Then, the discontinuity is fed with one of the previously computed modes, and the fields transmitted or reflected towards the discontinuity arms are matched to the modal fields corresponding to each output waveguide. This method allows one to compute the intrinsic transmission and reflection coefficients of the discontinuity (i.e., coefficients not altered by additional effects such as finite crystal size, etc.). The procedure is presented in detail using some simple discontinuities as test cases. Then, it is applied to the computation of the coupling from a waveguide to free space and for the analysis of a filtering T junction.

Journal Article↗

PubMed2002

Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies.

Multifocal occurrence and frequent recurrence are characteristic features of urothelial carcinomas of both the urinary bladder and the upper urinary tract. To describe the clonal nature of these tumors, 2 theories have been proposed. The monoclonality hypothesis describes the multiple tumors as descendants of a single genetically transformed cell spreading throughout the urothelium. In contrast, field cancerization caused by carcinogen exposure of the urothelium may lead to independent development of synchronous or metachronous nonrelated tumors at different sites of the urothelial tract. In the last 10 years, a multitude of molecular genetic studies have investigated the clonality of multifocal urothelial carcinomas. The majority of studies revealed a monoclonal origin of the multiple tumors. However, most of these studies investigated advanced invasive carcinomas. A small but significant proportion of multifocal urothelial carcinomas appear to arise from different clones, supporting the field-cancerization hypothesis. Oligoclonal tumors might be more common in precursor lesions and early tumor stages. The frequent monoclonality found in patients with advanced tumors could be due to outgrowth of 1 tumor cell clone with specific genetic alterations. Two important mechanisms appear to be important for the spread of malignant cells: intraluminal seeding and intraepithelial migration. Investigation of the entire urothelial lining in patients with urothelial tumors should provide further insight into the development of multifocal urothelial carcinomas.

Animals↗

PubMed2002

Multiple multipole method with automatic multipole setting applied to the simulation of surface plasmons in metallic nanostructures.

Highly accurate computations of surface plasmons in metallic nanostructures with various geometries are presented. Calculations for cylinders with irregular cross section, coupled structures, and periodic gratings are shown. These systems exhibit a resonant behavior with complex field distribution and strong field enhancement, and therefore their computation requires a very accurate numerical method. It is shown that the multiple multipole (MMP) method, together with an automatic multipole setting (AMS) procedure, is well suited for these computations. An AMS technique for the two-dimensional MMP method is presented. It relies on the global topology of each domain boundary to generate a distribution of numerically independent multipole expansions. This technique greatly facilitates the MMP modeling.

Journal Article↗