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Biomedical subjects

M Dietel

Publications and source records attributed to M Dietel.

At least 91 records · Page 5Linked to original sources
PubMed1998

Detection of oestrogen receptors in non-invasive and invasive transitional cell carcinomas of the urinary bladder using both conventional immunohistochemistry and the tyramide staining amplification (TSA) technique.

In a retrospective immunohistochemical study, the expression of oestrogen receptors has been investigated in paraffin-embedded transitional cell carcinomas of the urinary bladder with antibody 6F11, using both a conventional immunohistochemical detection system and the highly sensitive tyramide staining amplification (TSA) technique. The study comprised 88 invasive and 97 non-invasive carcinomas of 101 female (mean age 68.4 years) and 84 male (mean age 68.2 years) patients. Oestrogen receptors were detected in 34 (18 per cent) carcinomas with conventional immunohistochemistry and 46 (25 per cent) with TSA. Using TSA, oestrogen receptors were significantly more often detectable in invasive (32/88) than in non-invasive carcinomas (14/97) and in G2/G3 (37/122) rather than in G1 (9/63) carcinomas. There were no associations between patients' age and sex and the expression of oestrogen receptors. The functional significance of oestrogen receptor expression in a subset of transitional cell carcinomas of the urinary bladder remains to be determined.

Adult↗
PubMed1998

Genomic alterations associated with malignancy in head and neck cancer.

BACKGROUND: Comparative genomic hybridization (CGH) was performed on 50 primary head and neck squamous cell carcinomas (HNSCC) to discover molecular genetic alterations underlying the progression of these tumors. METHODS: In CGH, equal amounts of differently labeled tumor deoxyribonucleic acid (DNA) and normal reference DNA were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities were quantitated separately as gray levels along the single chromosomes. The over- and underrepresented DNA segments were determined by computation of ratio images and average ratio profiles. RESULTS: Prevalent changes observed in more than 50% of the HNSCC included deletions of chromosomes 1p, 4, 5q, 6q, 8p, 9p, 11, 13q, 18q, and 21q and DNA overrepresentations of 11q13 as well as 3q, 8q, 16p, 17q, 19, 20q, and 22q. The calculation of ratio profiles of tumor subgroups revealed that well differentiated carcinomas (G1) were defined by the deletions of chromosomes 3p, 5q, and 9p together with the overrepresentation of 3q, suggesting the association with early tumor development. Accordingly, the undifferentiated tumors (G3) were characterized by additional deletions of chromosomes 4q, 8p, 11q, 13q, 18q, 21q, and overrepresentations of 1p, 11q13, 19, and 22q. CONCLUSION: Our data indicate that the CGH patterns of chromosomal imbalances may help to define the malignant potential of head and neck squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1998

High-dose rate interstitial with external beam irradiation for localized prostate cancer--results of a prospective trial.

PURPOSE: A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. MATERIALS AND METHODS: Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). RESULTS: Before starting treatment, a PSA value of > or =10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was < 1.0 ng/ ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73. 1% (38/ 52) of patients, respectively. A positive biopsy combined with a PSA value of > 1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. CONCLUSION: The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.

Adenocarcinoma↗
PubMed1998

Angiomyxoma of the umbilical cord in one twin with cystic degeneration of Wharton's jelly. A case report.

We report the prenatal diagnosis of an angiomyxoma of the umbilical cord in a female fetus of a dizygotic twin pregnancy. The pregnant woman was hospitalized at 18 weeks for exclusion of a suspected exomphalos. Using high-resolution ultrasound and color doppler, the umbilical tumor (8 x 5 x 4 cm) was suspected to be an angiomyxoma without malformations in the fetus. Neither chromosomal aberrations nor elevated alphafetoprotein were found after amniocentesis. Serial examinations showed an increase in the size of the cystic mass without deterioration of the fetal condition. Macroscopical and microscopical examinations of the tumor performed after delivery revealed an angiomyxoma with cystic degeneration of Wharton's jelly. Tumors of the umbilical cord are rare anomalies and should be considered when using prenatal ultrasound for detection of cystic lesions.

Adult↗
PubMed1998

Correlation of prenatal ultrasound diagnosis and morphological findings of fetal autopsy.

The findings of prenatal ultrasound diagnosis were compared with the autopsy findings in 183 fetuses (between the 14th and 24th week of gestation), aborted for fetal malformations in the period from 1995 to 1997. In these 183 cases, the primary diagnosis showed 50 central nervous system anomalies, 48 cardiovascular system anomalies, 42 genitourinary system anomalies, 18 respiratory system anomalies, 8 skeleton system anomalies, 6 gastrointestinal system anomalies and 11 other abnormalities. Of the total number of cases, 41% had multiple malformations. In 144 cases (78%), the prenatal diagnosis was confirmed by autopsy, in 36 cases (20%) the prenatal diagnosis was confirmed with additional significant pathology, and in only 3 cases (2%) the prenatally detected malformation was not confirmed by pathological examination. Autopsy remains an important component of the evaluation of fetal losses after induced abortion.

Autopsy↗
PubMed1998

Induction of apoptosis in the centre of multicellular tumour spheroids of colorectal adenocarcinomas--involvement of CD95 pathway and differentiation.

Multicellular tumour spheroids (MCTS) are three-dimensional cell culture systems which are widely used in cancer research. They are characterized by an outer zone of proliferating cells, an inner region of differentiating quiescent cells and an area of so-called necrotic cell death in their centre. The exact cause of this cell death, a controversy for many years, was the aim of the present study. Our data show that cell death in the centre of MCTS of three colorectal adenocarcinoma cell lines (HRT-18, HT-29 and CX-2) was induced by apoptosis. Apoptotic cells were initially distributed at random but accumulated very quickly in the quiescent and central area at day 4-5, suggesting a time- rather than size-dependent synchronization of apoptosis parallel to the formation of the proliferation gradient in MCTS. To study mechanisms inducing apoptosis, the Fas-pathway was investigated. A cell-cell contact-dependent expression of CD95 was found in all MCTS. FasL was not detected in monolayer cultures, but was expressed in spheroids of HRT-18 and CX-2. We found that TNF alpha and TGF beta 1 activated the CD95 pathway in all three cell lines. Since both TNF-alpha and TGF-beta are known to be inducible by hypoxia in a variety of cell types, we suggest that these hypoxia-induced factors sensitize the CD95 pathway in the quiescent area of MCTS. Furthermore, a loss of the heat shock proteins 27, 32, 60, 73 and 90 was observed in the quiescent area of spheroids. This suggests that tumour cell differentiation in the inner region of MCTS may be an additional factor inducing apoptosis.

Journal Article↗
PubMed1998

Allelic loss on chromosome 10q in human lung cancer: association with tumour progression and metastatic phenotype.

We analysed 78 carcinomas of the lung for allelic losses on chromosome 10q. The tumours were of different stage and grade and comprised 22 small-cell lung carcinomas (SCLC), 40 squamous cell carcinomas (SCC), 11 adenocarcinomas, four large-cell carcinomas and one carcinoid. They were investigated by six polymorphic markers located between 10q21 and 10qter. We observed a high incidence of loss of heterozygosity (LOH) in SCLC (91%) and metastatic SCC (56%). Non-metastatic SCC showed deletions in three cases (14%) and no LOH was found in the other types of non-small-cell lung cancer. The statistical analysis indicated that the presence of LOH correlated significantly with advanced tumour stages in the entire collective and in particular within the SCLC and SCC subgroups. For SCC, a positive association was found between LOH and metastases formation, while in SCLC the number of non-metastatic tumours was too small for a final conclusion. Whereas SCLC was frequently characterized by multiple allelic losses, suggesting the deletion of the entire chromosomal arm, SCC showed interstitial imbalances. A high incidence of allelic loss was observed between the markers D10S677 and D10S1223. The analysis of five informative cases suggested the presence of two non-overlapping regions between the loci D10S677/D10S1237 and D10S1213/D10S1223. In SCLC, we did not find mutations in the putative tumour-suppressor gene MXI1. The data indicate that LOH on chromosome 10q is associated with tumour progression in SCC and SCLC. Thus it may become a useful genetic marker in the assessment of the malignant potential of these tumour types.

Alleles↗
PubMed1998

Chromosome alterations in breast carcinomas: frequent involvement of DNA losses including chromosomes 4q and 21q.

Comparative genomic hybridization was applied to map DNA gains and losses in 39 invasive ductal breast carcinomas. Frequent abnormalities included gains on chromosomal regions 1q, 8q, 11q12-13, 16p, 19, 20q and X as well as frequent losses on 1p, 5q, 6q, 9p, 11q, 13q and 16q. Furthermore, frequent losses on 4q (20 cases) and 21q (14 cases) were found for the first time in this tumour type. High copy number amplifications were observed at 8q12-24, 11q11-13 and 20q13-ter. Highly differentiated tumours were associated with gains on 1q and 11q12-13 along with losses on 1p21-22, 4q, 13q, 11q21-ter. Undifferentiated breast carcinomas were characterized by additional DNA imbalances, i.e. deletions of 5q13-23, all of chromosome 9, the centromeric part of chromosome 13 including band 13q14 and the overrepresentation of chromosome X. We speculate that these changes are associated with tumour progression of invasive ductal breast cancer.

Breast Neoplasms↗
PubMed1998

[Effect of gene polymorphism on detoxifying glutathione-S-transferase enzymes on chromosomal stability of squamous epithelial carcinomas in the area of the head-neck].

BACKGROUND: While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk. MATERIAL AND METHODS: We examined genotype frequencies from leukocyte DNA of 269 laryngeal cancer patients, 123 pharyngeal cancer patients and 216 controls. Polymorphisms at different glutathione-S-transferase (GST) gene loci were investigated. Losses of heterozygosity (LOH) at 12 different chromosomal gene loci were determined in 37 of the study patients by comparing blood and tumor cell DNA. The relationship between high risk genotypes and the occurrence of LOH was investigated. RESULTS: Glutathione-S-transferase high risk genotypes were identified at the first and third genes of the M family (GSTM1, GSTM3) and the first gene of the P family (GSTP1). These high risk genotypes are seen to have a statistically significant influence on the occurrence of LOH in the tumor tissue. CONCLUSION: There is evidence that the polymorphisms studied play a role in the carcinogenic process by influencing the chromosomal fragility which may lead to the inactivation of tumor suppressor genes or the activation of oncogenes.

Alcohol Drinking↗
PubMed1998

Expression of the novel mitoxantrone resistance associated gene MXR7 in colorectal malignancies.

It was shown previously that a glypican encoding gene (MXR7/GPC3/OCl-5) was associated with mitoxantrone resistance in vitro. This study describes and investigation of an association between multidrug resistance and MXR7 in surgical cryo-specimens of 51 gastrointestinal tumors. The mRNA expression levels differ widely according to tumor species. In primary colorectal cancers, the level of MXR7 mRNA expression correlated loosely with the mRNA expression level of the multidrug-resistance-associated protein (MRP). In colorectal metastases an elevated MXR7 mRNkA expression level was observed when compared to primary colorectal carcinomas.

ATP-Binding Cassette Transporters↗
PubMed1998

Microscope remote control with an Internet browser.

OBJECTIVE: To develop a telemicroscopy system that is independent of specialized hardware and software for microscope remote control. DESCRIPTION OF THE SYSTEM: An automatic microscope mounted on a CCD camera was connected to a computer that fulfills the function of an internet server. Any internet user can access this server and can control the microscope by use of an internet browser with Java support. The system can be tested at http:@amba.rz.charite.hu-berlin.de/telemic. FUNCTION AND APPLICATIONS: The user can move the microscope stage, change the magnification or execute any other microscope operations by pressing buttons of the downloaded telemicroscopy client program. The new microscope images are transferred automatically. Structures of interest within the images can be highlighted and discussed online with other telemicroscopy clients. Any internet browser with Java support, like Netscape or Microsoft Internet Explorer, makes an internet user a telemicroscopy client and thus a possible consultant for telepathology. CONCLUSION: The internet telemicroscope offers new possibilities for telepathology. This development should promote communication between pathologists and may thus increase the quality of diagnosis.

Computer Communication Networks↗
PubMed1998

Use of antibodies against estrogen and progesterone receptors to identify metastatic breast and ovarian carcinomas by conventional immunohistochemical and tyramide signal amplification methods.

The immunohistochemical detection of estrogen receptors (ERs) and progesterone receptors (PRs) is useful for the differentiation of cytostatically treatable breast and ovarian carcinomas from other metastatic adenocarcinomas of unknown primary sites. We retrospectively studied metastases of 68 breast, 24 ovarian, 15 bronchogenic, 35 gastric, 22 pancreatic, 23 colonic, 27 renal cell, and 26 primary bronchogenic carcinomas by using a panel of 3 antibodies against ERs and 4 antibodies against PRs and applying both a conventional immunohistochemical detection method and the highly sensitive tyramide signal amplification (TSA) technique. Antibody 6F11 against ERs was slightly more sensitive than clone 1D5 with both detection methods, staining 5% more breast carcinomas and 4% more ovarian carcinomas with TSA, compared with conventional immunohistochemical analysis. Furthermore, clone 6F11 detected ERs in 4 of 26 primary bronchogenic carcinomas and 1 of 35 metastases of gastric carcinomas with conventional immunohistochemical techniques; an additional 9 primary and 6 metastatic bronchogenic carcinomas and 2 metastatic gastric carcinomas were positive with TSA. The resulting specificities for breast and ovarian carcinomas versus all other carcinomas were 0.97 with conventional immunohistochemical techniques and 0.85 with TSA. Antibody 1A6 against PRs was slightly more sensitive but least specific for breast and ovarian carcinomas (specificity was 0.96 with conventional immunohistochemical methods and 0.91 with TSA), compared with antibody hPRa3 and a polyclonal antibody (specificity was 1.00 with both detection methods). Antibodies TE111 against ERs and 10A9 against PRs were significantly less sensitive than the other antibodies. We conclude that TSA cannot be recommended for the detection of ERs and PRs to differentiate breast and ovarian carcinomas from other metastatic adenocarcinomas of unknown primary sites.

Antibodies, Monoclonal↗
PubMed1998

Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections.

The authors retrospectively tested the potential value of paraffin-reactive monoclonal antibodies (A103 against melan-A, T311 against tyrosinase) and antibody KBA62 as immunohistochemical markers for amelanotic metastatic melanomas. The study cases included 72 amelanotic metastases of known cutaneous melanomas, 59 poorly differentiated carcinomas, 73 sarcomas of varying histogenesis, 4 Leydig cell tumors, 10 high-grade lymphomas, and 6 plasmoblastic/anaplastic myelomas. The results were compared with immunostainings for S-100 protein and HMB-45. HMB-45, antimelan-A, and antityrosinase showed almost identical staining results, with a sensitivity of 0.85 for HMB-45 and of 0.86 for both antimelan-A and for antityrosinase. HMB-45 and antityrosinase both had a specificity of 1.00; the specificity of antimelan-A was 0.95 as a result of a positive reaction in three of three adrenocortical carcinomas and four of four Leydig cell tumors. KBA62 stainings resulted in a sensitivity of 0.86 for melanomas. A positive immunoreactivity of KBA62 alone had a specificity of only 0.83, but in conjunction with anti-S-100 protein (sensitivity, 1.00; specificity, 0.87) and anticytokeratin 8/18/19 (CK), a KBA62+/S-100+/CK- immunophenotype identified all except one of the melanoma cases that were negative for the three melanocyte-specific markers with a specificity of 0.99. In conclusion, we found comparable immunohistochemical sensitivities of HMB-45, antityrosinase, and antimelan-A for a highly specific identification of approximately 85% of amelanotic metastatic melanomas on paraffin sections. Melanomas that were negative for all of these specific markers might be sensitively and specifically detected with anti-S-100 protein and KBA62.

Antibodies, Monoclonal↗
PubMed1998

[Illegal professional conflict of interest from the viewpoint of university research].

The problem of illegal donations in favour of a medical faculty is complex since there exists a multi-layered network between the sponsors (public, private, industrial etc.) and the recipients (institutions, private persons, groups). The fields of interests are of course heterogeneous. The university needs the donation to perform research, the industry supports medicine to co-operate on the new development of drugs, techniques etc., the country needs both since otherwise there will be no innovative new products and thus no modern new jobs etc. to regulate these interactions, there are many regulations and decrees which may contradict each other. Transparency is the matter of cure, at least for medical universities. This means that all donations should be processed by accounts of the university or associated foundations. This should be open to the public that no inappropriate advantage can be taken personally. The University Hospital Charité for example has announced clear regulations for the scientists which they can follow easily to avoid unintended mistakes. It must be clarified to for the sponsors and the public that the financial support is clearly directed to stimulate and improve science--only this justifies our research work.

Conflict of Interest↗