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Biomedical subjects

Gian Kayser

Publications and source records attributed to Gian Kayser.

At least 19 recordsLinked to original sources
PubMed2006

Lymphangiogenesis and its regulation in human neuroblastoma.

For the first time, we could detect lymph vessels in neuroblastoma (NB) by immunohistochemistry with the antibody D2_40. Furthermore, we demonstrate expression of the lymphangiogenic factors VEGF-C and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in NB in vitro and in vivo by RT-PCR. However, addition of recombinant human VEGF-C or -D results in the absence of autocrine growth stimulus in NB cells. Treatment of NB cells with retinoic acid did not lead to a change in VEGF-C or VEGF-D mRNA expression. Incubation of the NB cells Lan-5 with 5-Aza-2'-deoxycytidine led to the up-regulation of VEGF-C mRNA expression, suggesting that the promotor of VEGF-C is methylated. Finally, VEGF-C mRNA expression could be effectively down-regulated by transfection with a specific siRNA in the NB cells Kelly. We conclude that lymphangiogenesis is involved in NB biology and that siRNA directed against VEGF-C may have a future role in anti-lymphangiogenic strategies in NB.

Humans↗
PubMed2006

Neuroendocrine differentiation and neuroendocrine morphology as two different patterns in large-cell bronchial carcinomas: outcome after complete resection.

BACKGROUND: In 1999, large-cell neuroendocrine carcinoma of the lung was introduced by the World Health Organization (WHO) as a new tumor entity in the group of non-small cell, epithelial tumors, a differentiated classification of neuroendocrine tumors of the lung not existing until this time. Scientific knowledge on prognosis and therapy of these tumors, especially between those with neuroendocrine morphology only and those showing additional expression of neuroendocrine markers, is fragmentary. In this analysis, we studied the clinical behavior and the prognosis of these two rare tumor entities. PATIENTS AND METHODS: The analysis comprises 12 patients of a total of 2053, who underwent thoracotomy for non small-cell lung carcinoma between 1997 and 2005 in the Department of Thoracic Surgery at the University Hospital of Freiburg. Clinical data, pathological examinations as well as complete follow-up were reviewed from large-cell carcinoma with neuroendocrine morphology only (n=4) and from large-cell carcinoma expressing neuroendocrine markers (n=8). RESULTS: The median survival of patients with neuroendocrine morphology was 30 months (11-96 months). In the patient group showing the expression of neuroendocrine markers, the median survival time was 20 months (2-26 months). Tumor recurrences occurred in the group with neuroendocrine morphology, without exception, in the form of distant metastases and in the group with neuroendocrine markers as intrapulmonary metastases. CONCLUSION: Large-cell neuroendocrine carcinomas of the lung show aggressive behavior with a poor prognosis. Expression of neuroendocrine markers markedly reduce tumor-free interval as well as survival and might influence the site of metastases.

Journal Article↗
PubMed2006

Grid technology in tissue-based diagnosis: fundamentals and potential developments.

Tissue-based diagnosis still remains the most reliable and specific diagnostic medical procedure. It is involved in all technological developments in medicine and biology and incorporates tools of quite different applications. These range from molecular genetics to image acquisition and recognition algorithms (for image analysis), or from tissue culture to electronic communication services. Grid technology seems to possess all features to efficiently target specific constellations of an individual patient in order to obtain a detailed and accurate diagnosis in providing all relevant information and references. Grid technology can be briefly explained by so-called nodes that are linked together and share certain communication rules in using open standards. The number of nodes can vary as well as their functionality, depending on the needs of a specific user at a given point in time. In the beginning of grid technology, the nodes were used as supercomputers in combining and enhancing the computation power. At present, at least five different Grid functions can be distinguished, that comprise 1) computation services, 2) data services, 3) application services, 4) information services, and 5) knowledge services. The general structures and functions of a Grid are described, and their potential implementation into virtual tissue-based diagnosis is analyzed. As a result Grid technology offers a new dimension to access distributed information and knowledge and to improving the quality in tissue-based diagnosis and therefore improving the medical quality.

Journal Article↗
PubMed2006

Radiation-induced leiomyosarcoma of the oropharynx.

Leiomyosarcoma is a malignant mesenchymal tumor originating from smooth muscle cells, which most frequently develops in the myometrium and in the gastro-intestinal tract. Reviewing the international literature, radiation-induced sarcoma arise in 0.035 to 0.2% of all irradiated patients. Especially in the head and neck region, radiation-induced leiomyosarcoma is an extremely rare lesion. The authors report a case of a radiation-induced leiomyosarcoma of the tonsillar region of the oropharynx in a 51-year-old male patient, who had undergone radiation therapy of this region 38 years before. The lesion was treated by radical surgery. Diagnostic steps, histological presentation and therapy are described in detail and the literature concerning radiation induced malignancies in general as well as radiation induced leiomyosarcoma in particular is reviewed. The highlights of this case are an extremely uncommon location and a rare pathological entity of radiation induced malignancies.

Journal Article↗
PubMed2006

Towards an automated virtual slide screening: theoretical considerations and practical experiences of automated tissue-based virtual diagnosis to be implemented in the Internet.

AIMS: To develop and implement an automated virtual slide screening system that distinguishes normal histological findings and several tissue--based crude (texture-based) diagnoses. THEORETICAL CONSIDERATIONS: Virtual slide technology has to handle and transfer images of GB Bytes in size. The performance of tissue based diagnosis can be separated into a) a sampling procedure to allocate the slide area containing the most significant diagnostic information, and b) the evaluation of the diagnosis obtained from the information present in the selected area. Nyquist's theorem that is broadly applied in acoustics, can also serve for quality assurance in image information analysis, especially to preset the accuracy of sampling. Texture-based diagnosis can be performed with recursive formulas that do not require a detailed segmentation procedure. The obtained results will then be transferred into a "self-learning" discrimination system that adjusts itself to changes of image parameters such as brightness, shading, or contrast. METHODS: Non-overlapping compartments of the original virtual slide (image) will be chosen at random and according to Nyquist's theorem (predefined error-rate). The compartments will be standardized by local filter operations, and are subject for texture analysis. The texture analysis is performed on the basis of a recursive formula that computes the median gray value and the local noise distribution. The computations will be performed at different magnifications that are adjusted to the most frequently used objectives (*2, *4.5, *10, *20, *40). The obtained data are statistically analyzed in a hierarchical sequence, and in relation to the clinical significance of the diagnosis. RESULTS: The system has been tested with a total of 896 lung cancer cases that include the diagnoses groups: cohort (1) normal lung--cancer; cancer subdivided: cohort (2) small cell lung cancer--non small cell lung cancer; non small cell lung cancer subdivided: cohort (3) squamous cell carcinoma--adenocarcinoma--large cell carcinoma. The system can classify all diagnoses of the cohorts (1) and (2) correctly in 100%, those of cohort (3) in more than 95%. The percentage of the selected area can be limited to only 10% of the original image without any increased error rate. CONCLUSION: The developed system is a fast and reliable procedure to fulfill all requirements for an automated "pre-screening" of virtual slides in lung pathology.

Journal Article↗
PubMed2006

Lack of CD117 and rare bcl-2 expression in stomach cancer by immunohistochemistry. An immunohistochemical study with review of the literature.

BACKGROUND: Gastric adenocarcinoma is one of the most frequent malignancies worldwide including Iran. This study was designed to immunohistochemically evaluate the CD117 and bcl-2 expression in gastric carcinomas and their potential use as therapeutic targets in the treatment of patients with advanced stage gastric cancer. MATERIALS AND METHODS: Representative paraffin blocks obtained from 38 operated gastric adenocarcinoma patients were retrieved from Afzalipour Hospital pathology department archive, Kerman, Iran. Immunohistochemical analysis (IHC) for CD117 was carried out in all cases including negative (normal gastric epithelium) and positive (Gastrointestinal Stromal Tumor) controls. In addition, the cases were evaluated immunohistochemically for apoptosis-related protein (bcl-2), to evaluating a potential association of CD117 expression with the cell proliferation regulatory pathways. RESULTS: No positive reaction for CD117 was seen in gastric carcinoma tumor cells irrespective to the cell type, grade, and stage, proliferation and apoptosis rate. Expression of bcl-2 was observed in only one case. CONCLUSION: We conclude that CD117 overexpression detectable by immunohistochemistry does not play a significant role in gastric carcinoma pathways and development, although overexpression at the gene level and/or mutated CD117 expression might exist. Thus, it is unlikely that the CD117 pathway is of clinical significance in gastric carcinoma patients.

Journal Article↗
PubMed2006

Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer.

Dysregulation of the centrosome complex and chromosomal segregation has been associated with aneuploid cells and aggressive solid tumours, but the relevance of this mechanism to the adenoma-carcinoma sequence of sporadic colorectal cancer (sCRC), especially tumours showing chromosomal instability (CIN), is still unknown. In a series of matching normal epithelial cells (n = 41), dysplastic cells (n = 18), and invasive carcinoma cells (n = 41) from cases with sCRC, mRNA levels of the centrosomal kinase Aurora-A/STK15 and the chromosomal passenger- and cell cycle-associated molecules Incenp, Survivin, Mad-2, and Cyclin-D1 were therefore measured with specific reference to the type of genetic instability. Compared with normal epithelium, significant up-regulation of mRNAs was already present for Aurora-A/STK15 (p = 0.0313) in dysplastic cells and for all investigated markers in invasive carcinoma. Whereas Aurora-A/STK15 mRNA levels were similarly up-regulated in dysplastic and invasive carcinoma cells (p = 0.0797), Survivin (p = 0.0046) and Cyclin-D1 (p = 0.0017) mRNA levels increased from dysplastic to invasive carcinoma cells. In carcinomas, Incenp mRNA correlated with T category (p = 0.0149), and Survivin (p = 0.0382) and Cyclin-D1 (p = 0.0185) were associated with tumour differentiation. Importantly, a significantly higher (p = 0.0419) fold-change of Aurora-A/STK15 mRNA (p = 0.0419), but not Incenp, Survivin, Mad-2 or Cyclin-D1, was observed in sCRC cases with CIN (n = 29) when compared with tumours showing microsatellite instability (MIN, n = 10). The present data are the first to show an early increase of the centrosomal kinase Aurora-A/STK15 in the adenoma-carcinoma sequence of sCRC. The regulation of this kinase differs in CIN- and MIN-type sCRCs and the pattern of changes is different from those of the cell-cycle-associated markers Survivin, Mad-2, and Cyclin-D1. This reinforces the concept of preferential dysregulation of the centrosome complex in CIN-type (aneuploid), compared with MIN-type, sporadic colorectal cancers and may influence the response to and efficiency of novel therapeutics targeting Aurora kinases.

Adenoma↗
PubMed2006

Theory and implementation of an electronic, automated measurement system for images obtained from immunohistochemically stained slides.

OBJECTIVE: To develop and implement an Internet-based, automated image measurement system for immunohistochemically stained slides including fluorescence images in online and off-line modes. STUDY DESIGN: An image analyzing system was developed that automatically measures digitized images obtained from immunohistochemically stained slides. It is divided into a common server platform and a specific image quantification system based upon DIAS (University of Jena). After registration, the user fills in an input data form and attaches images to be measured. The server periodically transfers the data to the measurement system. The measurement works on dynamic thresholding and active sampling of objects visualized by fluorescence and conventional chromogens. It includes stereologic algorithms, object quantification, syntactic structure analysis and quality assurance. RESULTS: The system has been tested for diaminobenzidene, alkaline phosphatase and fluorescence images (FITC, etc.). The reproducibility and stability of the system are > 98%. The series of successfully measured images comprises > 1,000 images in total in the online and off-line modes. CONCLUSION: An Internet-based automated image measurement system has been developed that offers worldwide access to the major requests for quantification of immunohistochemically stained slides-tissue array analysis, nuclear stains (MIB, hormones), membrane stains (CerbB2), vascularization and fluorescence in situ hybridization.

Anatomy, Cross-Sectional↗
PubMed2006

Sclerosing hemangioma of the lung: a benign tumour with potential for malignancy?

Pulmonary sclerosing hemangioma represents a rare neoplasm with variable potential for progression. This case report of a 35-year-old female with left-sided thoracic pain. Computed tomography revealed a centrally located, well-circumscribed and partially calcified lesion. Intraoperative findings were suggestive of a carcinoid tumour. The tumour was completely removed by lobectomy followed by systematic lymphadenectomy. The histopathological analysis revealed a sclerosing hemangioma, a rare benign neoplasm. Sclerosing hemangiomas (SHs) are true neoplasms derived from alveolar pneumocytes. However, little data is available on the potential malignant behaviour, such as lymphnode metastases, local recurrence, and the appearance of SH's. Generally, wedge resection is justified in the majority of cases, but in cases of uncertain intraoperative diagnosis, anatomic resection with systematic lymphadenectomy is recommended.

Adult↗
PubMed2005

Numerical and structural centrosome aberrations are an early and stable event in the adenoma-carcinoma sequence of colorectal carcinomas.

AIMS: Numerical and structural centrosome changes have been described for and linked with genetic instability in solid tumors. Here, we specifically address centrosome aberrations in the adenoma-carcinoma sequence of colorectal cancer by detailed evaluation of gamma-tubulin staining patterns. METHODS: Formalin-fixed and paraffin-embedded specimens (normal colonic epithelium n=21; low-grade intraepithelial neoplasia n=27, high-grade intraepithelial neoplasia n=16 and invasive adenocarcinomas n=33) were stained by an anti-gamma-tubulin antibody using standard immunofluorescence. Three-dimensional image stacks of the stainings were recorded (Zeiss LSM510 confocal microscope), followed by numerical and structural data analysis (DIAS software package) and statistical evaluation (NCSS-software). RESULTS: The mean centrosome signal per cell differed significantly (P<0.0001) between normal colonic epithelium (0.8775) and each low-grade intraepithelial neoplasia (1.787), high-grade intraepithelial neoplasia (2.259) and invasive carcinomas (2.267). Similarly, both the centrosomes' structural entropy (SE) and minimal spanning tree (MST) differed significantly (P<0.001) between normal (SE=3.956, MST=38.78) and each low- (SE=6.39, MST=26) and high-grade intraepithelial neoplasia (SE=5.75, MST=26.97) and invasive carcinoma (SE=6.86, MST=28.08). CONCLUSION: Numerical and structural centrosome dysregulation is seen as early as in low-grade dysplastic lesions of the adenoma-carcinoma sequence of colorectal carcinomas and may, as such, play an initial role in the carcinogenic process.

Adenocarcinoma↗
PubMed2005

Lung carcinoma-associated atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa.

This article analyzes phenotype and genotype alterations of the lung in association with lung cancer. The frequency of phenotype preneoplastic lesions (atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD)) was analyzed at distinct distances from the tumor boundary in 150 lung carcinomas. AAH was noted in 19/150 (13%) cases and more frequently seen in adeno carcinomas, squamous cell dysplasia was noted in 46/150 (31%) cases and more frequently seen in squamous cell carcinomas. The degree of cellular atypia decreased with increasing distance from tumor boundary in both AAH and SCD. At similar distances, genotype (chromosome) alterations of surrounding bronchial mucosa were studied in additional 55 primary and secondary lung tumors by karyotype analysis. Numerical chromosome aberrations occur frequently in primary lung carcinomas and adjacent bronchial mucosa, and affect at average 4.5/10 metaphases in primary lung cancer and 2/10 metaphases in metastases. Most abnormal metaphases were induced by chromosome losses, only few by additional copies, i.e. trisomy, etc. Losses of y chromosome were seen in both malignancy and adjacent bronchial mucosa, and interpreted as "tumor related", losses of chromosome 21 in adjacent bronchial mucosa were non-tumor related in adenocarcinoma and metastases, losses of chromosome 19 in adjacent bronchial mucosa occurred independently in squamous cell and large cell carcinomas. The data suggest the hypothesis that preneoplastic lesions in the lung might be partly induced by the tumor itself.

Aged↗
PubMed2004

Teleconsultation in diagnostic pathology: experience from Iran and Germany with the use of two European telepathology servers.

Eighty pathology cases were sent independently to each of two telepathology servers. Cases were submitted from the Department of Pathology at the University of Kerman in Iran (40 cases) and from the Institute of Pathology in Berlin, Germany (40 cases). The telepathology servers were located in Berlin (the UICC server) and Basel in Switzerland (the iPATH server). A scoring system was developed to quantify the differences between the diagnoses of the referring pathologist and the remote expert. Preparation of the cases, as well as the submission of images, took considerably longer from Kerman than from Berlin; this was independent of the server system. The Kerman delay was mainly associated with a slower transmission rate and longer image preparation. The diagnostic gap between referrers' and experts' diagnoses was greater with the iPATH system, but not significantly so. The experts' response time was considerably shorter for the iPATH system. The results showed that telepathology is feasible for requesting pathologists working in a developing country or in an industrialized country. The key factor in the quality of the service is the work of the experts: they should be selected according to their diagnostic expertise, and their commitment to the provision of telepathology services is critical.

Germany↗
PubMed2004

New developments in digital pathology: from telepathology to virtual pathology laboratory.

AIMS: To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. PRESENT STATUS: Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). FEATURES OF VIRTUAL PATHOLOGY: A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under development and does not completely fulfil the requirements of a conventional pathology institution at present. VIRTUAL PATHOLOGY AND E-LEARNING: At present, e-learning systems are "stand-alone" solutions distributed on CD or via internet. A characteristic example is the Digital Lung Pathology CD (www.pathology-online.org), which includes about 60 different rare and common lung diseases and internet access to scientific library systems (PubMed), distant measurement servers (EuroQuant), or electronic journals (Elec J Pathol Histol). A new and complete data base based upon this CD will combine e-learning and e-teaching with the actual workflow in a virtual pathology institution (mode a). The technological problems are solved and do not depend upon technical constraints such as slide scanning systems. PERSPECTIVES: Telepathology serves as promotor for a new landscape in diagnostic pathology, the so-called virtual pathology institution. Industrial and scientific efforts will probably allow an implementation of this technique within the next two years.

Artificial Intelligence↗
PubMed2003

Vascular diffusion density and survival of patients with primary lung carcinomas.

AIM: To investigate the clinical significance of tumour vascularisation in operated lung cancer patients. MATERIALS AND METHODS: Histological slides obtained from 498 patients with potentially curative operated lung carcinomas in two different institutions of thoracic surgery were immunohistochemically stained with an anti-CD34 antibody and subjected to quantitative image analysis. Syntactic structure analysis measured the absolute and relative features of vessels, including the numerical tumour cells densities relative to their nearest neighbouring vessel. These data are associated with tumour volume, post-surgical TNM stage, and each patient's survival. RESULTS: The clinical data, including sex distribution, age of patients, pTNM stages and survival, did not differ between the two institutions. The tumour vascularisation (volume fraction, Vv) amounted to 7% in lung carcinomas, was independent from cell type and increased in advanced tumour stages (pT4, pN3). Advanced tumour stages presented with a higher numerical vascular density and with maintained minimum diameter and circumference of vessels. Each patient's survival was closely associated with the pN stage, tumour volume, cell type and numerical density of tumour cells within a distance less than 20 micro m from the nearest neighbouring vessel due to multivariate statistical analysis. CONCLUSION: Vascularisation of lung tumours becomes altered in advanced tumour stages. Of prognostic significance is the distribution of tumour cells in relation to the nearest neighbouring vessel only.

Adenocarcinoma↗
PubMed2003

Giant-cell reparative granuloma of the temporal bone: a case report and review of the literature.

Giant-cell reparative granuloma (GCRG) is an unusual, non-neoplastic fibrous lesion that most often arises in the mandible and maxilla. GCRG of the temporal bone is exceedingly rare. To the best of our knowledge, only 17 cases have been previously reported in the international medical literature. Although no case of metastasis has been reported, this malignancy can be locally aggressive, and it often recurs following incomplete excision. We report the case of a young woman with a very large GCRG of the right temporal bone. We discuss the clinical picture, differential diagnosis, histologic evaluation, appearance on computed tomography and magnetic resonance imaging, and treatment options. We also review the cases of temporal bone GCRG that have been reported in the literature so far.

Adolescent↗
PubMedDate not supplied

Association of galectin-1- but not galectin-3-dependent parameters with proliferation activity in human neuroblastomas and small cell lung carcinomas.

BACKGROUND: Galectins, a family of animal lectins binding beta-galactosides, are involved in growth regulation of diverse cell types in vitro, even harboring the potential to act as biphasic modulators with cell type selectivity. Owing to this capacity they might affect tumor growth when expression is adapted adequately. MATERIALS AND METHODS: To determine galectin-1-/-3- related features in routinely-fixed sections of two tumor types with poor prognosis (neuroblastoma and small cell lung carcinoma), immuno- and lectin histochemistry with specific antibodies and labeled galectins was performed. RESULTS: In comparison to previously studied tissue culture models, galectin-3 was frequently present, documenting occurrence of discrepancies between tumor models and clinical material for this protein. Cytoplasmic staining with galectin-1 and its antibody coincides with the proliferative activity of positive tumor cells determined by the MIB-1 monoclonal antibody. No statistical correlation was seen for galectin-3. CONCLUSION: These results encourage further cell biological studies to assess a regulatory role of galectin-1 on cell growth in vitro as a model for interfering with tumor proliferation by modulating expression of this type of endogenous effector(s).

Antigens, Differentiation↗