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K Wilgenbus

Publications and source records attributed to K Wilgenbus.

6 recordsLinked to original sources

Correlation of clinical data with proteomics profiles in 24 patients with B-cell chronic lymphocytic leukemia.

The development of human cancer is caused by complex molecular perturbations leading to variable clinical behavior often even in single disease entities. To prove that expression profiling on the protein level can be correlated with clinical data we systematically compared in a pilot study the protein expression patterns obtained by 2-dimensional gel electrophoresis with clinical features in human B-cell chronic lymphocytic leukemia (B-CLL), a disease characterized by broad clinical variability. Statistical methods were devised to analyze the spot pattern from 24 patient samples. This analysis allowed the identification of proteins that clearly discriminated between the patient groups with defined chromosomal characteristics or whose expression levels did correlate with clinical parameters such as patient survival. This report demonstrates that the correlation of large-scale protein expression profiles with clinical data can be used to gain new insights into molecular aspects of a disease. The data described here show that B-CLL patient populations with shorter survival times exhibit changed levels of redox enzymes, heat shock protein 27 and protein disulfide isomerase. These molecules may be potentially involved in drug resistance.

Humans↗

Mapping of the breakpoints on the short arm of chromosome 17 in neoplasms with an i(17q).

Isochromosomes are monocentric or dicentric chromosomes with homologous arms that are attached in a reverse configuration as mirror images. With an incidence of 3-4%, the i(17q) represents the most frequent isochromosome in human cancer. It is found in a variety of tumors, particularly in blast crisis of chronic myeloid leukemia (CML-BC), acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and medulloblastoma (MB), and indicates a poor prognosis. To determine the breakpoints on the molecular genetic level, we analyzed 18 neoplasms (six CML, four AML, one NHL, and seven MB) with an i(17q) and two MB with a pure del(17p) applying fluorescence in situ hybridization (FISH) with yeast artificial chromosome (YAC) clones, P1-artificial chromosome (PAC) clones, and cosmids from a well-characterized contig covering more than 6 Mb of genomic DNA. We identified four different breakpoint cluster regions. One is located close to or within the centromere of chromosome 17 and a second in the Charcot-Marie-Tooth (CMT1A) region at 17(p11.2). A third breakpoint was found telomeric to the CMT1A region. The fourth, most common breakpoint was detected in MB, AML, and in CML-BC specimens and was bordered by two adjacent cosmid clones (clones D14149 and M0140) within the Smith-Magenis syndrome (SMS) region. These results indicate that the low copy number repeat gene clusters which are present in the CMT and SMS regions may be one of the factors for the increased instability that may trigger the formation of an i(17q).

Adolescent↗

Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha.

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.

Acanthosis Nigricans↗

[EBV in malignant lymphomas].

PCR and in-situ-Hybridization were used to detect EBV-DNA within Hodgkin- and Non-Hodgkin-Lymphomas. By the use of primers for the Bam H1 W fragment we could show EBV-DNA to be associated with 45% Hodgkin- and 25% T-Lymphomas, whereas we could not find EBV-DNA within B-Lymphomas. In about one third of the PCR-positive cases we could localize EBV-DNA mostly in the tumor cell nuclei by in-situ-hybridization.

Base Sequence↗

[Eye changes in acanthosis nigricans maligna--possible effect of growth factors in the etiopathogenesis of this paraneoplastic disease picture].

A 64-year-old white male presented to our hospital with hyperplastic tarsal and to a lesser degree bulbar conjunctivae. Approximately one month later the full clinical picture of acanthosis nigricans maligna developed. In addition to ectropia of the lower eyelids he showed madarosis; neither the linea grisea nor the lacrimal points were discerneable. On gastroscopy a diffusely growing gastric adenocarcinoma adjacent to the cardia was found and later confirmed histopathologically. The computertomography of the abdomen demonstrated one solitary metastasis to one parapancreatic lymphnode. It is generally assumed that in the course of paraneoplastic syndroms products secreted by the tumor induce changes in the target organs, e.g. the conjunctiva and the skin. In the presented case (1) southern blot analysis of the tumor tissue proved an increase of Epidermal Growth Factor-receptors, (2) immunohistochemistry showed prominent staining for Transforming Growth Factor-alpha. In conclusion, this case is suggestive of a possible link between growth factors and acanthosis nigricans maligna.

Acanthosis Nigricans↗

[DNA extraction and Southern blot analysis in paraffin embedded material].

DNA was extracted from formaldehyde fixed and paraffin embedded tissue by the use of a modified extraction protocol. In all cases the recovered DNA was more degraded than DNA from fresh or frozen tissue. Fixation times of more than 4 days made it impossible to use the extracted DNA for Southern Blotting; DNA from paraffinized tissues not older than 1 or 2 years could be used for Southern Blotting after digestion with restriction enzymes, but we did not succeed in showing bands with restriction fragments more than 10 kb in length. We conclude that SBA analysis for malignant lymphomas with DNA extracted from routinely paraffin-embedded tissues isn't possible, because the restriction fragments looked for are in many cases longer than 10 kb.

Blotting, Southern↗