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Biomedical subjects

K Günther

Publications and source records attributed to K Günther.

At least 37 records · Page 2Linked to original sources
PubMed2001

Benign solitary fibrous pleural tumour. Evidence of primitive features and complex genomic imbalances, including loss of 20q.

AIMS: Cytogenetic data on solitary fibrous tumours (SFT) are very limited. We studied a benign pleural SFT for its ultrastructural and immunohistochemical details, and made cytogenetic analyses for comparison with other genetic and ultrastructural studies of SFT. RESULTS: Immunohistochemistry showed strong positivities for CD34 and vimentin, but no reactions with anti-cytokeratins and epithelial membrane antigens. Electron microscopy revealed primitive desmosomes in our SFT. The results thus evinced fibroblast-like cells with intermediate epithelial-mesenchymal character. Comparative genomic hybridization of the tumour revealed losses of 1p33-->pter, 17pter q21, entire copies of chromosomes 19 and 22, and gains of 1p21-p22, 2q23-q32.3, 3pl2-q13.2, 4p14-q28, 6p12-q21, 9p21-->pter and 13q21-q31. Furthermore, there was loss of 20q, as was previously reported elsewhere in a case of benign and a case of malignant SFT. CONCLUSIONS: The results furnish further evidence of the involvement of -20q in SFT. In addition, they show that SFT may have complex genomic imbalances and primitive features, despite having a benign appearance.

Chromosome Deletion↗
PubMed2001

Transcription of cytokeratins 8, 18, and 19 in bone marrow and limited expression of cytokeratins 7 and 20 by carcinoma cells: inherent limitations for RT-PCR in the detection of isolated tumor cells.

The suitability of "real-time" quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8, CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone marrow specimens from noncancer patients, and 30 bone marrow specimens from patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow specimens from noncancer patients demonstrated background transcription of CK8 (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1 copies/10(3) copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly lower. When maximal background values were used as a threshold value to define positivity in tumor cell dilution experiments, sensitivity levels of one tumor cell in 10(4) bone marrow cells were determined for CK7 and CK20 RT-PCR assays. Maximal background expression values of the different CKs as obtained in the control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times (CK7) in bone marrow specimens from cancer patients, with none of these specimens exceeding the maximal background expression value of CK8. We conclude that RT-PCR for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor cells in bone marrow of cancer patients. On the other side, the limited number of gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that assay sensitivity for these CKs might be limited because of their selective expression by carcinoma cells.

Animals↗
PubMed2001

Multiple primary malignancies: An epidemiological and pedigree analysis of 57 patients with at least three tumours.

AIM AND METHODS: Data of our patients with at least three primary malignancies were retrospectively analysed to detect any remarkable patterns which might be of interest for follow-up or early tumour detection and to identify a possible hereditary cancer predisposition. From 1.1.1954 to 1.8.1995 57 patients (0.1%) among a grand total of 52 398 cancer patients had a minimum of three malignancies. RESULTS: The 5-year survival rates after colorectal, bladder, prostate, uterine corpus and gastric cancer were higher than those seen in patients with the corresponding solitary tumours. In both sexes, the mean interval between the individual tumours was greater (4.0 years) between the first and second tumours than between the second and third (2.5 years). In women, the intervals were roughly twice as long (6.8 and 3.7 years) as in men (3.7 and 2.0 years). 40.4% (n=23/57) had a colorectal, 28.1% (n=16) a bladder, and 41.7% (n=15/36 men) had a prostate carcinoma. 66.7% (n=14/21 women) contracted at least one gynaecological tumour. In 24 families HNPCC, in one a Li-Fraumeni Syndrome, and in another Hereditary Diffuse Gastric Cancer was suspected.

Adult↗
PubMed2001

Trisomy 8 as sole karyotypic aberration in an ovarian metastasizing Sertoli-Leydig cell tumor.

Sertoli-Leydig cell tumors (SLCTs) represent a rare group of sex-cord stromal tumors of the ovary of unknown pathogenesis. We report a SLCT of intermediate differentiation with peritoneal recurrence and lymph node metastasis 12 months after removal, including cytogenetic analysis by comparative genomic hybridization and fluorescence in situ hybridization, which showed trisomy 8 as sole unbalanced karyotypic aberration. Our results provide evidence that a simple numeric chromosomal abnormality in SLCT may be associated with a malignant phenotype and suggest that the molecular pathogenesis of SLCT may be different from ovarian granulosa-stromal cell tumors.

Adolescent↗
PubMed2001

Detection of invasion-related chromosomal changes in highly and weakly invasive melanoma cell clones by a modified comparative genomic hybridization approach.

Invasion is a key step in the systemic spread of tumour cells. The aim of this study was to investigate whether specific chromosomal aberrations in melanoma occur during acquisition of a strongly invasive phenotype. We previously selected highly and weakly invasive cell clones from the human melanoma cell line Mel Im. Both cell clones retained a stable phenotype over more than 40 passages, revealing a five-fold difference in their invasive potential in vitro. Direct comparative genomic hybridization (CGH) (modified CGH) of the two cell clones was used as a powerful tool to screen for different chromosomal aberrations in both clones. Standard CGH and fluorescence in situ hybridization (FISH) was performed to verify the results of this improved technique. In general, the CGH pattern showed a high degree of identity consistent with the fact that the cell lines represent subclones of the same cell line. However, a few defined changes between the two cell clones were observed, including loss of 1q21-qter, 4q, 11p14-pter, 19q and 20p in the highly invasive cell clone. Two of the regions (1q and 11p) have already been suggested to be involved in melanoma progression, whereas changes in the others have not been detected before. In summary, our direct CGH approach proved to be suitable for fast and direct comparison of two cell types and allowed the identification of two known and three novel chromosomal changes involved in the acquisition of a strongly invasive melanoma cell phenotype.

Cell Line↗
PubMed2000

Genomic structure and DNA binding properties of the human zinc finger transcriptional repressor AP-2rep (KLF12).

We recently cloned a novel murine transcriptional repressor, the Krüppel-like zinc finger protein AP-2rep (HGMW-approved symbol KLF12), that binds to a regulatory element in the AP-2alpha gene promoter. In the present study, we characterize the human AP-2rep homolog and describe expression patterns in human urogenital and lymphoma cell lines. The predicted human protein of 402 amino acids exhibits 95.8% identity and 98.5% similarity to the murine AP-2rep peptide. The genomic locus of human AP-2rep consists of seven exons and was assigned to chromosome 13q22 by fluorescence in situ hybridization to metaphase chromosomes. Human AP-2rep repressed both reporter expression from a transiently transfected AP-2alpha promoter and the endogenous AP-2alpha gene and inversely was negatively regulated by AP-2alpha. The consensus motif CAGTGGG was identified by an in vitro binding site selection assay. In summary, our data further point to an important role of AP-2rep as a transcriptional silencer and reveal reciprocal regulation of AP-2alpha and AP-2rep.

Amino Acid Sequence↗
PubMed2000

p27(kip1) expression in rectal cancer correlates with disease-free survival.

BACKGROUND: The cell-cycle inhibitor p27(kip1) is a potential tumor suppressor and might serve as a prognostic marker in rectal cancer, in particular with regard to patient selection for adjuvant therapy. MATERIALS AND METHODS: Immunohistochemical analysis was performed, using an anti-p27(kip1) monoclonal antibody, on paraffin sections of two matched [age, gender, UICC stage, year of operation (1982-1991)] groups of patients (n = 2 x 82) with rectal carcinoma curatively treated by surgery alone. The groups differed only in subsequent metachronous distant metastatic spread. All patients had to meet the selection criterion "free of local disease," in order to exclude surgical influence. Follow-up was prospective (median of 74 months). The intensity of staining (-, +, ++, ) and rate of positive cells (as a percentage of total tumor volume) were judged separately for cytoplasms and nuclei. RESULTS: On multivariate analysis, cytoplasmic staining intensity proved to be the best prognostic factor of disease-free survival and approached statistical significance (P = 0.0552, Cox regression). On univariate analysis, considering cytoplasmic staining alone, intensely stained ( ) tumors showed significantly poorer disease-free survival (vs ++, +, -; Kaplan-Meier, logrank, P = 0.0185). CONCLUSIONS: The demonstrated correlation between cytoplasmic compartmentalization of p27(kip1) and increased metastatic spread as well as disease-free survival underscores the role of p27(kip1) in rectal cancer. However, since other reports emphasize the importance of nuclear p27(kip1) expression, the mechanisms of steady-state and subcellular distribution of p27(kip1) remain unclear, and further investigation is needed.

Adenocarcinoma↗
PubMed2000

[Hereditary colonic carcinoma without polyposis (HNPCC) without satisfying the Amsterdam criteria].

Epidemiologic data suggest that an underlying genetic disposition can be detected in up to 10% of all colorectal cancer patients and autosomal dominantly inherited hereditary non-polyposis colorectal cancer (HNPCC) is the entity most frequently identified. It was described first by A. Warthin in 1895 in "Family G" and is characterized by a predisposition to an early onset of colorectal cancer and other intestinal or genitourinary tumors. We report the case of a 61-year-old woman with five different cancers. Although the strict Amsterdam Criteria were not fulfilled, molecular analysis revealed HNPCC; further genetic testing in the family confirmed that the 36-year-old and so far healthy son had inherited the germline mutation of his affected mother. Genetic testing in clinically suspected HNPCC cases is recommended for patients with colorectal cancer meeting the Amsterdam Criteria. In patients meeting one of Bethesda Criteria 2-7 without meeting the Amsterdam Criteria, germline mutation analysis is recommended only in MSI-positive tumors.

Adult↗
PubMed2000

D3 lymph node dissection in gastric cancer: evaluation of postoperative mortality and complications.

Since November 1995 we have been performing a D3 lymph node dissection in patients undergoing an operation for gastric cancer with a curative intent. The aim of the present study was to evaluate whether this procedure results in an increased postoperative mortality or complication rate in a Western population. Between November 1995 and August 1997 the postoperative courses of 76 patients were retrospectively assessed (45.3 lymph nodes per patient, lymph node ratio: 0.16). The patient outcome was compared with data from a historic control group of patients (n = 383) in whom the newly established D2 dissection was studied in our department. Regarding the demographic, clinical, and tumor-pathologic data, and the choice of resection and reconstructive procedures, the two groups differed only slightly. The postoperative mortality of 1% was lower (vs 6.8%) while the overall complication rate of 34% (vs 32.1%) was identical. In particular, no anastomotic leakage (vs 9.4%) and fewer nonsurgical complications (17.1% vs 27.9%) occurred. The reoperation rate was 1% vs 9.7%. However, in 6% of the patients drainage tubes had to be inserted under computed tomographic guidance. The average hospital stay remained unchanged (21.9 vs 20.7 days). A D3 dissection was shown to be feasible while demonstrating no disadvantages in the patients when compared with the D2 procedure.

Adenocarcinoma↗
PubMed2000

Benign metastasizing leiomyoma: a cytogenetically balanced but clonal disease.

Benign metastasizing leiomyoma (BML) is a rare condition, characterized by the occurrence of multiple smooth-muscle nodules, most often located in the lung after previous hysterectomy because of histologically benign appearing leiomyoma. Although the condition resembles a metastatic process, case studies provided evidence that it may be the result of an intravenous leiomyomatosis or an independent and multifocal smooth-muscle proliferation. Comparative genomic hybridization and X-chromosome inactivation analysis were used in a case of BML to determine whether pulmonary and uterine tumors are related one to another. A balanced karyotype, previously reported in leiomyomas and an identical X-chromosome inactivation pattern found in all tumorlets, is most consistent with a monoclonal origin of both uterine and pulmonary tumors and the interpretation that pulmonary lesions are metastatic.

Adult↗
PubMed2000

Interphase cytogenetics of multicentric renal cell tumours confirm associations of specific aberrations with defined cytomorphologies.

To demonstrate associations of certain chromosomal aberrations with defined renal cell tumour (RCT) subtypes, we analysed 239 tumour nephrectomy cases for specimens with multicentric tumours. Chromosomal in situ hybridization was then performed on 15 cases with 34 foci (16 conventional renal cell carcinomas (RCCs), and 18 papillary RCTs (11 carcinomas and seven adenomas) for specific chromosomal aberrations, using alpha-satellite probes for chromosomes 3, 7 or 17. Particular preference was given to cases which had separate foci with different cytomorphologies. Furthermore, we compared aberrations in relation to tumour size, stage, grade and between different foci in a specimen. Thirty-four cases had multiple tumours. Forty-seven per cent of the multicentric tumours were conventional RCCs and 53% papillary RCTs (against 83% solitary conventional RCCs and 5% solitary papillary RCTs). Three conventional RCCs sized 8 mm (G3), 13 cm (pT2, G2) and 15 cm (pT3b, G3), respectively, revealed monosomy 3, and 13 were disomic. Seventeen papillary RCTs (11 carcinomas and six adenomas) displayed trisomy 17, irrespective of size or grade. Four papillary carcinomas and six papillary adenomas had trisomy 7, and the rest (seven papillary carcinomas and one papillary adenoma) revealed disomy 7. In conclusion, papillary RCTs were tendentially multicentric. Although specific for conventional RCCs heedless of size, monosomy 3 was only observed in high-grade and/or advanced tumours. Trisomy 17 was only detectable in papillary RCTs irrespective of tumour state, showing increased copies with tumour growth. Papillary RCTs also appeared to lose some copies of chromosome 7 with tumour progress, possibly reflecting malignancy.

Carcinoma, Papillary↗
PubMed2000

Training of junior rowers before world championships. Effects on performance, mood state and selected hormonal and metabolic responses.

BACKGROUND: Few data have been published on training of competitive athletes and about metabolic, hormonal and psychological reactions to overreaching (transient over-training) and tapering in successful athletes. METHODS: Training was recorded and effects on mood state and metabolic and hormonal responses were examined in 10 rowers and spares of the coxed eight during preparation for the World Championships 1995. Mood state was determined using the Recovery-Stress-Questionnaire for Athletes. Resting morning blood parameters as well as performance were measured every week over a period of five weeks. RESULTS: Very high training loads of approximately 3.2 hours per day were sustained for 18 days. Maximum performance (Pmax) and maximum lactate (Lamax) were decreased during high-load training phases (overreaching), Pmax, Lamax and endurance increased after the tapering period. There were decreases in gonadal and hypothalamic steroid hormones (fsh, 1h, prolactin, testosterone) during overreaching and increases in these hormones in tapering. Both performance and hormonal indices of training load were reflected by deterioration of recovery in the Recovery-Stress-Questionnaire for Athletes. CONCLUSIONS: Clear signs of overreaching were found after 18 days of intense training of about 3 h.d(-1) in these highly-trained athletes, i.e. decreases in performance, gonadal and hypothalamic steroid hormones and deterioration of recovery in the psychological questionnaire. After tapering values returned to baseline values before the World Championship. The findings indicate that overreaching is an integral part of successful training regimens and can be analyzed by a multi-factorial approach involving biological and psychometric data.

Adolescent↗
PubMed1999

Expression and function of beta(1) and beta(3) integrins of human mesothelial cells in vitro.

Mesothelial cells (MC) and extracellular matrix (ECM) components are thought to play a pivotal regulatory role during the inflammatory-reparative response of serosal membranes. Integrins are known to serve as cellular ECM receptors, but mesothelial integrin expression and its function, particularly its role for attachment to different ECM components, remain to be elucidated. The aim of the present study was to characterize the integrin expression of human omentum majus derived MC (HOMC) in vitro by immunohistochemistry and to investigate their functional significance with regard to HOMC adhesion to fibronectin (fn), vitronectin (vn), collagen IV (coll IV), and laminin (ln). Mesothelial cells in vitro strongly expressed beta(1), beta(3), alpha(2), alpha(3), alpha(5), and alpha(v) chains. A weak reactivity was found for alpha(1) and alpha(6), but no alpha(4) reactivity was detectable. Compared to the control, fn, vn, coll IV, and ln caused a significant 2.6-, 2.2-, 2-, and 1.6-fold increase of HOMC adhesion, respectively. Inhibition studies revealed that HOMC attachment to fn is mediated by alpha(5)beta(1), alpha(v)beta(1), and alpha(v)beta(3), with a synergistic effect of alpha(5)beta(1) and alpha(v)beta(3). Adhesion to vn is mediated by alpha(v)beta(1) and alpha(v)beta(3). Integrins alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) mediate adhesion to coll IV and ln. We suggest that the integrin expression and function of mesothelial cells described here play an important role in the interaction of MC with the ECM, particularly during the acute and chronic inflammatory-reparative response of serosal membranes.

Antigens, CD↗
PubMed1999

Diagnostic relevance of chromosomal in-situ hybridization in Merkel cell carcinoma: targeted interphase cytogenetic tumour analyses.

AIMS: To resolve the conflicting diagnoses of five pathologists (which included well-differentiated neuroendocrine carcinoma, malignant carcinoid, undifferentiated small-cell carcinoma, primitive neuroectodermal tumour, metastases of small-cell lung carcinoma (SCLC) and Merkel cell carcinoma (MCC)), and tumour-free lungs after necropsy, we investigated an alarmingly metastasizing MCC in a 32-year-old Caucasian man using chromosomal in-situ hybridization (CISH). Differences in incidence and course in males and females also prompted targeted analyses for chromosomes X and Y. The lesion was also analysed for p53 gene mutations. METHODS AND RESULTS: Paraffin sections of the thorax, buccal lymph nodes and scalp tumours were stained with haematoxylin and eosin. Immunohistochemistry was performed with antibodies against pancytokeratin, keratin 20, neuron-specific enolase (NSE), chromogranin, neurofilaments and vimentin, among others. Sections (5-6 microm) of the tumours were analysed with alpha-satellite probes for chromosomes 1, 6, 7, 11, 12, 17, 18, X and Y using CrSH; and exons 5-9 of the p53 gene were examined by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) methods. Although positive for pancytokeratin, keratin 20, chromogranin, NSE, synaptophysin and vimentin, the similarity in antigen profiles expressed by SCLC and MCC prevented a definitive tumour diagnosis. Chromosomal in-situ hybridization, however, revealed trisomies 1 and 11, two frequent aberrations in MCC, and trisomy 18. Moreover, 71% of the tumour cells had two to three copies of X, whereas 98% of the cell nuclei in the hair follicles and normal epidermis (purported Merkel cell origins) displayed one X chromosome. No mutations were detected in the five exons of the p53 gene examined. CONCLUSIONS: Had CISH been performed earlier, treatment may have been tailored specifically to suit MCC, since MCC and SCLC have different therapeutic strategies. Finally, chromosome X may be of prognostic relevance in MCC, which apparently predominates in females and yet shows poorer prognosis in males, and hence be worthy of further investigation.

Adult↗
PubMed1999

A proven de novo germline mutation in HNPCC.

Hereditary non-polyposis colon cancer (HNPCC) is a heterogeneous group of tumour predisposition syndromes caused by germline mutations in at least four different mismatch repair genes. HNPCC patients are prone to the development of carcinomas of the intestinal tract and other specific sites. Identification of presumptive HNPCC patients is primarily based on a positive family history of colorectal cancer in at least two generations. In the course of mutation screening of the MLH1 and MSH2 genes in patients manifesting a carcinoma of the HNPCC tumour spectrum before the age of 45 years, we identified a germline MSH2 344delA frameshift mutation in a male proband. This index patient, at the age of 25 years, initially developed a large rectal adenoma that was removed by polypectomy. Ten years later he was operated on for an invasive right sided colon carcinoma in the caecum (International Union Against Cancer (UICC) stage III). The mother and father, aged 61 and 66 years, respectively, were healthy and had no family history of colorectal cancer. Subsequent molecular analyses excluded the germinal MSH2 344delA alteration identified in their son and at the same time paternity was confirmed with a set of informative polymorphic markers. Thus, the genetic alteration identified in our patient definitely represented a de novo germline mutation in one of the major HNPCC genes. This case report of a patient with colorectal cancer at a relatively young age with no family history is intended to encourage mutation screening of the MSH2 and MLH1 genes in similar cases to find out whether this group of patients contains an increased proportion of de novo mutations in mismatch repair genes.

Adaptor Proteins, Signal Transducing↗