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K Kayser

Publications and source records attributed to K Kayser.

191 records · Page 11Linked to original sources

Evaluation of histochemical anthracyclin binding as potential prognostic parameter in small cell lung cancer.

In the quest to define further prognostic indicators for small cell lung cancer we have combined standard prognostic evaluation of several tissue and serum markers with monitoring the capacity of tumor cells to bind a carrier-immobilized anthracyclin at the time of diagnosis. The prospective study on 150 patients with small cell lung cancer (SCLC) was performed including the performance of immunohistochemical analysis [neuron-specific enolase (NSE), keratin, and vimentin], and serum marker measurements [NSE, carcinoembryonic antigen (CEA), and CYFRA], flanked by compilation of data on clinical staging at the time of diagnosis, cytostatic drug regimen, remission rates, and survival of the patients. As innovative test substance we synthesized and histochemically exploited carrier-immobilized doxorubicin. The cohort includes 108 men and 42 women grouped into stage I (limited disease: 69 patients; median survival: 317 days), stage IIa (extensive disease IIa: 19 patients; median survival: 244 days), and stage IIb (extensive disease IIb: 62 patients; median survival: 202 days). An oat-cell type was diagnosed in 112 patients, an intermediate cell type in 32 patients, and a combined cell type in 6 patients. Immunohistochemically, 123 tumors (82%) were positive for NSE, 75 tumors (50%) positive for keratin, and 26 tumors (18%) positive for vimentin. In 101 tumors (67%) specific intracellular binding of doxorubicin could be detected. Elevated serum levels for CEA and NSE were associated with an unfavorable prognosis of the corresponding patients (CEA, 261 days vs 467 days; NSE, 316 days vs 414 days). 137 patients received chemotherapy (median survival: 356 days) and 13 patients were not treated (median survival: 119 days). The six patients with the combined cell type and other patients with negative tumor specimen concerning the capacity to bind the anthracyclin were subject of a significantly shortened survival period irrespective of the cytostatic regimen (277 days vs. 381 days). Despite the current uncertainty of the biochemical nature of the histochemically detectable binding, the technical feasibility of the given interdisciplinary approach encourages to further pursue the documentation of anthracyclin binding.

Antibiotics, Antineoplastic↗

Expression of endogenous lectins (galectins, receptors for ABH-epitopes) and the MIB-1 antigen in esophageal carcinomas and their syntactic structure analysis in relation to post-surgical tumor stage and lymph node involvement.

Squamous cell carcinomas of the esophagus, a disease with poor prognosis, are especially frequent in China and South Africa. To initiate the study of endogenous lectins in this tumor class we employed synthetic neoglycoconjugates and focused on galectins as markers. Histological sections of 43 cases of esophageal carcinomas were analyzed with labeled galectins-1 and -3 and their specific antibodies, neoglycoconjugates exposing chemically prepared histo-blood group A-, B- and H-trisaccharides and the antibody MIB-1 (Ki-67). Features of structural and numerical staining intensities determined quantitatively were correlated to clinical data sets of pTN stages, sex and age of patients. Low tumor stages (pT1/T2) were seen in 10/43 cases (23%) and 65% of the carcinomas surgically treated lacked notable lymph node involvement (pN0). The women were younger than the men (47 years versus 54 years). The proliferation activity of the tumor cells was high and amounted to 75% at average. The presence of galectin-1 and the structural entropy of distribution of staining with carrier-immobilized A-trisaccharide were associated with pN stages. These initial data indicate that distinct glycohistochemical features appear to have prognostic significance in this tumor class, adding to the emerging significance of this marker class in lung cancer.

ABO Blood-Group System↗

Lectin (WGA)-dependent superoxide anion release by neutrophils as a prognostic factor in lung cancer.

This study was performed to explore whether lectin-induced generation of superoxide anions by neutrophils, lectin-induced degranulation of these cells and NO-synthase activity in pleural effusions can be used as prognostic factors of primary lung cancer patients. Among the activities tested, increased generation of superoxide by Triticum vulgaris agglutinin (WGA)-activated neutrophils showed prognostic relevance. Thus, this lectin-dependent reactivity of immune cells warrants further investigation in addition to the histochemical analysis.

Cell Degranulation↗

From telepathology to virtual pathology institution: the new world of digital pathology.

Telepathology has left its childhood. Its technical development is mature, and its use for primary (frozen section) and secondary (expert consultation) diagnosis has been expanded to a great amount. This is in contrast to a virtual pathology laboratory, which is still under technical constraints. Similar to telepathology, which can also be used for e-learning and e-training in pathology, as exemplarily is demonstrated on Digital Lung Pathology (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories will be implemented in the near future: a) those with distributed pathologists and distributed (> or = 1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists (usually situated in one institution) and a centralized laboratory, which digitizes complete histological slides. Both scenarios are under intensive technical investigations. The features of virtual pathology comprise a virtual pathology institution (mode a) that 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 and number of transferred images have to be limited, and usual different magnifications have to be used. The sender needs to possess experiences in image sampling techniques, which present with the most significant information. 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. The first experiences of a virtual pathology institution group working with the iPATH server working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalization of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalization is still under development. Virtual pathology can be combined with e-learning and e-training, that will serve for a powerful daily-work-integrated pathology system. At present, e-learning systems are "stand-alone" solutions distributed on CD or via Internet. A characteristic example is the Digital Lung Pathology CD, which includes about 60 different rare and common lung diseases with some features of electronic communication. These features include access to scientific library systems (PubMed), distant measurement servers (EuroQuant), automated immunohisto-chemistry measurements, or electronic journals (Elec J Pathol Histol, www.pathology-online.org). It combines e-learning and e-training with some acoustic support. A new and complete database 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. At present, telepathology serves as promoter for a complete 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 with exciting diagnostic and scientific perspectives.

Computer Communication Networks↗

Elucidation of similarities of sugar receptor (lectin) expression of human lung metastases from histogenetically different types of primary tumors.

Selective interplay between proteins and carbohydrates of cellular glycoconjugates offers the potential to mediate physiologically important biorecognition and biosignaling, relevant to metastasis formation. Biotinylated neoglycoproteins were therefore employed as tools to detect endogenous sugar receptors (lectins) in paraffin-embedded sections of 35 lung metastases from different types of primary tumors. The selection consisted of 17 cases of sarcoma, 11 cases of testicular germ cell tumor, 5 cases of adenocarcinoma, 1 case of melanoma and 1 case of adamanthioma. Receptors with specificity to rhamnose, structurally related to galactose, and N-acetyl-D-galactosamine were present in all or clusters of tumor cells in 27 or 26 of 35 cases. Binding of other carbohydrate constituents of glycoconjugates and of heparin was comparatively lower, ranging from 13 out of 35 cases for L-fucose to 21 out of 35 cases for sialic acid. Regardless of the origin of hte metastatic lesions, the proportions of sugar receptor expression of tumor cells in lung metastases were similar, when the two probes with highest overall extent of binding to tissue sections were applied. Although the influence of the identical microenvironment should not be overlooked, tumor cell homing to a certain target organ may supposedly be reflected in similarities of their profile of receptors for neoglycoproteins, carrying the glycohistochemically decisive constituents of naturally occurring glycoconjugates.

Biotin↗

Progress in telepathology.

The basic principles, technical objectives and future aspects of telecommunication in pathology (telepathology) are discussed. Visual information, which is the usually the basic source of medical disease classification, and its transfer have to be distinguished from acoustic information, which is commonly of secondary, i.e. abstract nature. Visual telecommunication in pathology can be applied in five different aspects, namely: a) to create visual data bases, b) to be used in expert consultation, c) to combine morphological and clinical data, d) to quantitate morphological findings (DNA- measurements, etc.), and e) to install remote control microscopes. Depending upon the application, different technical prerequisites and constraints have to be taken into account: queries of visual data bases and expert consultations can be performed by use of "normal" telephone lines; combination of morphological and clinical data and quantitation of morphological data may need a digitized telephone network (ISDN), and the transfer of live images needed for application of remote control microscopes can only be performed by use of ISDN or broadband networks (optical fiber transmission systems, satellite communication, etc.). The experiences of various groups working in different aspects of telepathology are described.

Forecasting↗

Integrated optical density and entropiefluss (current of entropy) in bronchial carcinoma.

Histological sections of formalin-fixed, paraffin-embedded bronchial carcinomas comprising 241 surgical specimens (lobes and lungs) were Feulgen stained. The integrated optical density of the nuclei (IOD) and the minimum distance between their centers of gravity (DG) was measured with an automated image analyzing system consisting of a TV camera connected to a personal computer via a frame grapper. Intratumorous lymphocytes served as DNA standard (2C peak), and 300 nuclei were measured at minimum. The entropy of the IOD, the percentage of S-phases (PS) of tumor cells with an IOD > 3C and > 5C, and the 2CV mean standard deviation were measured. According the theory of thermodynamically open systems, the entropiefluss (current of entropy) was defined by the gradient IOD/time through the surface of the tumors which can be approximated by the formula IOD*PS*DG/tumor volume. The following results were obtained: a) IOD of bronchial carcinoma is not associated with tumor size or lymph node infiltration (pT and pN stage). b) The minimum distance between tumor cells decreases with increasing tumor stage and increasing lymph node stage (pT, pN stage). c) The entropiefluss is low in limited and advanced tumor stages, and highest in tumors at moderately progressive tumor stages (pT2, pT3, pN1, pN2). Thus, in accordance with the theory of thermodynamically open systems, the entropiefluss reflects the "biological activity" of bronchial carcinoma.

Bronchial Neoplasms↗

Aids of telepathology in intra-operative histomorphological tumor diagnosis and classification.

Visual telecommunication (telepathology) was applied for expert consultation in intra-operative frozen sections and tumor classification of paraffin-embedded, poorly differentiated bronchial carcinoma. The Institute of Pathology, Hospital Baumgartnerhöhe, Vienna and the Department of Pathology, Thoraxklinik, Heidelberg transmitted histological images by use of commercially available computerized modems (VP 2000) and conventional telephone lines. The expert consultation of the frozen sections included the clinical history, macroscopic findings and problems of final judgement of the images. Additional useful information could be obtained in about 35% of cases, and comprised expansion of differential diagnosis, certainty of final diagnosis, and side findings, such as concurrent inflammation, sarcoid-like lesions, etc. The time required for intra-operative diagnosis was 6-10 min. Cases of the Austrian-German quality control study on lung cancer with divergent tumor classification were discussed by use of telepathology. A final congruent tumor diagnosis could be obtained in all divergent cases. The data indicate that telepathology can be successfully used for expert consultation of intra-operative frozen sections and panel discussions of difficult bronchial carcinoma cases.

Humans↗

Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy.

Superoxide production by neutrophils is believed to contribute to the efficiency of the host defence system. This activity is stimulated by the mannose-specific lectin concanavalin A, the N-acetylglucosamine/neuraminic acid-specific wheat germ agglutinin and the galactoside-specific lectins from Viscum album and human placenta. To assess whether this aspect of immune function is affected in cancer patients without or with treatment, neutrophil preparations from 69 patients were examined. Reductions in O2.(-)-production were observed for bronchial carcinoma patients after incubation with concanavalin A and the human lectin, while samples from breast cancer patients without or with treatment exhibited no significantly altered activity in the presence of each of the four agglutinins. Chemotherapy of lung and colorectal carcinoma patients reduced the neutrophilic response to concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens from other carcinoma types and from hemopoietic malignancies, there is no general impairment of responsiveness. In addition to the property of the lectin, the large extent of interindividual variation should be taken into account when it is attempted to enhance this factor of the host defence system against infections and malignant cells.

ABO Blood-Group System↗

Role of basic fibroblast growth factor in prostatic tumors.

Compared with normal prostatic tissue, the level of basic fibroblast growth factor (bFGF) is elevated in prostatic tumors. This suggests that bFGF may play a role in the development of prostatic neoplasms. The current study was undertaken to identify the cellular distribution of bFGF in benign prostatic hyperplasia (BPH) and prostatic carcinoma using a polyclonal antiserum against recombinant bFGF. In paraffin sections of prostatic tumors immunoreactive bFGF was found in fibroblasts, smooth muscle cells, and endothelial cells. Distinct staining was seen in most nuclei of these cells and a less intense immunoreaction occurred in the cytoplasm of smooth muscle cells. No immunostaining was seen in prostatic epithelial cells of prostatic tumors whether benign or malignant. With digoxigenin-labeled oligonucleotides in nonradioactive in situ hybridization, the presence of mRNA for bFGF was shown in smooth muscle cells of the stroma, suggesting that these cells are the main source of bFGF in BPH. Because no immunostaining for bFGF was obtained in the carcinoma cells, a specific role for bFGF cannot be seen for the development of malignant prostatic tumors.

Base Sequence↗

Expression of galactosyltransferase in prostatic tumors.

Galactosyltransferase (GalTase) has been discovered on a variety of cells where it is believed to be involved in cell-cell adhesion and cell-substratum adhesion as well as in metastasis of carcinoma cells. This immunohistochemical study was undertaken to identify the topography and the cellular distribution of GalTase in normal prostatic tissue, benign prostatic hyperplasia (11 cases), and prostatic carcinoma (26 cases). Immunoreactive GalTase was found to be exclusively associated with carcinoma cells and with premalignant epithelial cells in prostatic hyperplasia. In highly differentiated carcinomas, most of the carcinoma cells are positive for GalTase, whereas in poorly differentiated tumors, GalTase immunoreactivity was restricted to a subset of carcinoma cells with obviously invasive behavior. At the cellular level, GalTase was localized in the cytoplasm and at the cell membrane. In sections of normal prostatic tissue, as well as in unaltered acini of prostatic hyperplasic tissue, GalTase was not expressed. Fibroblasts, smooth muscle cells, and endothelial cells of the prostatic stroma were also consistently negative. With the use of immunoblots, we could confirm the presence of GalTase with a molecular mass of 45 kDa in the extracts of benign prostatic hyperplasic tissue and in prostatic carcinoma tissue but not in normal prostatic tissue. The results of our immunohistochemical study suggest that GalTase is a valuable marker to diagnose neoplastic transformation in prostatic tissue.

Blotting, Western↗