Biomedical subjects

G Seitz

Publications and source records attributed to G Seitz.

At least 73 records · Page 4Linked to original sources

PubMed1996

Chromosomal findings and p53-mutation analysis in chromophilic renal-cell carcinomas.

The chromosomal pattern of 31 specimens of chromophilic renal-cell cancer (RCC), selected according to the criteria mentioned in the classification of Thoenes and Störkel, is presented. A high male preponderance was found (8.7:1). Cytogenetic analysis revealed a typical pattern of numeric alterations specific for this sub-type in the majority of cases (i.e., --Y,+7, +12, +16, +17, and/or +20), which is different from the chromosomal patterns found in other sub-types of RCC. Gain of chromosome 20, as well as loss of the extra copy of chromosome 17 or loss of 17p, was found to be related to the higher-grade chromophilic carcinomas. None of the 14 cases examined by SSCP analysis revealed mutations of the p53 gene, indicating that other genes at 17(p) might be important in the progression of this sub-type of RCC.

Adult↗

PubMed1996

Isolation and characterization of the human mismatch repair gene hMSH2 promoter region.

Hereditary nonpolyposis colorectal cancer (HN-PCC) is one of man's commonest hereditary diseases. Several studies have identified four responsible genes that are involved in a process known as DNA mismatch repair; hMSH2 is the most important of these four genes. In addition to mutational analysis of these genes, investigations of transcriptional regulatory mechanisms are important. Therefore, our purpose has been to isolate the hMSH2 promoter region. Using direct sequencing of P1 recombinant DNA we have characterized 1100 bp of the hMSH2 promoter.

Base Sequence↗

PubMed1996

A second trefoil protein, ITF/hP1.B, is transcribed in human breast cancer.

Trefoil proteins form a specific group of stable secreted polypeptides. They are expressed in a lot of human cancers and during inflammatory processes of the gastrointestinal tract. Recently a new human trefoil protein, ITF/hP1.B, was isolated. Until now no studies of the activity of this gene in human solid tumors exist. In our examination we show for the first time that this gene is transcribed in human breast cancer. In contrast to another trefoil protein, pS2, the expression of ITF/hP1.B is not under control of estrogen in the human breast cancer cell line MCF-7. We suggest that the gene activity of ITF/hP1.B in addition to pS2 expression may be an improved prognostic marker in human breast cancer.

Biomarkers, Tumor↗

PubMed1995

[Carbohydrate-deficient transferrin. A new, highly specific marker for chronic alcohol consumption].

To test the value of carbohydrate-deficient transferrin (CDT) as a marker for chronic alcohol consumption, its concentration was measured in the serum of 74 patients (48 men, 26 women; mean age 48 [18-71] years) with various alcohol-related liver diseases, ten patients (six men, four women; mean age 61 [24-90] years) with non-alcohol related liver diseases and 30 healthy controls (12 men, 18 women; mean age 37 [19-84] years). In the healthy women the mean CDT concentration was 19.7 +/- 6.1 U/L, in healthy men 15.4 +/- 4.1 U/l (P < 0.05). The upper limit of normal (mean + 2 standard deviations) was 31.9 U/l in women and 23.6 U/l in men. Serum CDT levels were significantly raised in chronic alcohol abuse, depending on the degree of liver damage. The CDT level in alcohol-dependent women without liver disease was 31.1 +/- 4.3 U/l (P < 0.05), while in those with liver damage it was 42.3 +/- 14.2 U/l (not significant). The mean CDT concentration in male alcoholics without liver damage was 35.5 +/- 5.0 U/l (P < 0.01 compared with controls). In male alcoholics with liver damage the mean CDT level was 53.4 +/- 9.0 U/l (P < 0.001). In none of the ten patients with non-alcohol related liver disease was the CDT level above the upper limit of normal. The sensitivity of CDT as a marker for chronic alcohol consumption was 57% (42% for women, 65% for men) with a 100% specificity. For serum-gamma-glutamyl transferase the sensitivity was 87%, but its specificity only 73%. Because of its high specificity the serum CDT level is an added useful marker for demonstrating chronic alcohol consumption.

Adult↗

PubMed1995

Rearrangement of chromosome 1 is a frequent finding in endometrial carcinoma. An in situ hybridization study in nine endometrial carcinomas.

Nine endometrial carcinomas were examined for numerical aberrations of the chromosomes 1,7, and X by fluorescence in situ hybridization using highly repetitive chromosome-specific probes. In addition, a combination of a centromeric and a telomeric chromosome 1 probe was applied to detect structural chromosome 1 aberrations. Chromosome aberrations were found in six tumors. In four of these, an imbalance between 1q12 and 1p36 was detected, indicating the presence of an extra 1p- chromosome. In regard to the chromosomes 7 and X, monosomies and trisomies were found. Intratumoral genetic heterogeneity in endometrial carcinomas was detectable by FISH and flow cytometry. In conclusion, our findings confirm that chromosome 1 is frequently involved in structural chromosome changes, indicating chromosome 1 to be of importance in the evolution of endometrial carcinoma.

Adenocarcinoma↗

PubMed1995

Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression.

Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.

3-Iodobenzylguanidine↗

PubMed1995

[Endosonography of the esophagus and mediastinum].

It was only the endoscopic ultrasonography that allowed the esophagus and posterior mediastinum to be accessible to ultrasonography. The esophageal wall may be presented in its different anatomic layers to a degree of precision unattained by any other imaging procedure. Being important in the esophagus, both the upper rim of the tumor and the infiltration depth can this way be prognosed correctly to about 85%. In consequence, this allows proceedings appropriate to the tumor stage within the bounds of a multimodal therapeutic concept of esophagus carcinomas. Impressions of the esophagus caused by mediastinal tumors are safely distinguished from intramural tumors. Multiple biopsies to get an examination specimen from a deeper layer should be performed under no other conditions than after endoscopic ultrasonographic examination and just for special questions. In the differential diagnosis of achalasia and peptic stenosis of the esophagus, endoscopic ultrasonography proved to be less efficient. As for bronchial carcinomas, conclusive hints may be drawn from transesophageal and intratracheal ultrasonography. However, due to limited possibilities of judgment caused by air-containing structures these methods are not firmly established in the preoperative staging.

Carcinoma, Bronchogenic↗

PubMed1994

Stromal expression of c-Ets1 transcription factor correlates with tumor invasion.

The stroma reaction has an important role in tumor growth, invasion, and metastasis. In various invasive human carcinomas, as well as in a mouse model for tumor invasion, transcripts encoding the transcription factor c-Ets1 were detected within stromal fibroblasts, whereas they were absent in epithelial tumor cells. This expression of c-Ets1 was often increased in fibroblasts directly adjacent to neoplastic cells. Endothelial cells of stromal capillaries were also positive for c-Ets1 expression. In contrast, fibroblasts of corresponding noninvasive lesions and of normal tissues were consistently negative. In cultured human fibroblasts stimulated by basic fibroblast growth factor and tumor necrosis factor alpha, the expression of c-Ets1 correlated with the accumulation of transcripts for potential target genes, collagenase-1 and stromelysin-1. The same correlation was observed in some of the invasive carcinomas investigated. These results suggest that c-Ets1 participates in the regulation of tumor invasion in vivo.

Adult↗

PubMed1994

Expression pattern of breast-cancer-associated protein pS2/BCEI in colorectal tumors.

Recently, several carcinomas of the gastrointestinal tract were tested for pS2/BCEI activity, a gene isolated from breast-cancer cells and coding for a small secreted peptide. In the latter tumors, its activity is under estrogen control; surprisingly, it was also found expressed in carcinomas of the stomach, biliary tract and pancreas. We have now investigated the expression of this gene in 64 colorectal carcinomas, 31 adenomas and 13 polyps in comparison with their matrix tissues by applying molecular (RNA analysis) and immunohistochemical (pS2 antibody) techniques. Positive pS2 immunostaining (ranging from focal to strong immunoreaction) was noted in 89% of human colon cancers, while 11% remained negative. Furthermore, all 40 transitional mucosae were strongly positive, whereas normal mucosa was negative. Of hyperplastic polyps, 68.2% displayed a significant immunoreaction, and 80.6% of adenomas were focally positive. Finally, 6 out of 16 cases showed significant pS2 transcription in Northern blot analysis. These data clearly indicate that the breast-cancer-associated pS2 protein also plays an as yet undetermined role in the tumorigenesis of human colorectal carcinomas.

Breast Neoplasms↗

PubMed1994

DNA aneuploidy in prostatic adenocarcinoma: a frequent event as shown by fluorescence in situ DNA hybridization.

Fluorescence in situ hybridization (FISH) using specific DNA probes for chromosomes 1, 7, 10, and Y was performed on 53 prostatic tissue samples obtained from 33 radical prostatectomy specimens and two benign control specimens. The 53 samples from carcinomatous prostates included 33 cancerous and 20 noncancerous samples. Additionally, four metastatic lymph node specimens were examined. Clonal chromosome abnormalities were observed in 78% of the tumors studied. They were detected in a higher proportion in stage pT2 and pT3 tumors (86% and 88%, respectively) compared with stage pT1 tumors (25%). No stage pT4 tumor was analyzed. There was evidence of remarkable focal intratumoral heterogeneity documented by the study of two samples from the same tumor in three of six cases. Comparing FISH determined ploidy patterns with DNA flow cytometry (FCM) in 22 samples, FISH showed aneuploidy whereas FCM showed none.

Adenocarcinoma↗

PubMed1994

PCR expression analysis of the estrogen-inducible gene BCEI in gastrointestinal and other human tumors.

A polymerase chain reaction (PCR) assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot) analysis. Presently, by using reverse transcription-PCR analysis, a series of primary tumor tissues and established tumor cell lines were tested for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene's product. The result demonstrate the superior sensitivity of PCR by indicating the gene's expression in cases where immunohistochemical testing remained negative.

Base Sequence↗

PubMed1994

Influence of high and low dietary magnesium levels on functional, chemical and morphological parameters of 'old' rats.

The effect of dietary magnesium deficiency has so far been studied preferentially in rapidly growing rodents or in adult animals. Since magnesium deficiency frequently occurs in elderly persons too, magnesium- and calcium-deficient diets were offered during 32 and 64 days to 'old' rats (34 months old, spontaneous mortality of 15 per cent). The calcium-deficient diet (2.5 per cent of the requirement) was well tolerated and no profound biochemical disturbances were noted. In contrast, dietary magnesium deficiency (12.5 per cent of the requirement) induced loss of body weight, formation of erythema, severe hypomagnesaemia and increase of tissue calcium levels. No seizures were noted and mortality did not increase, in contrast to growing magnesium-deficient rats. Histologically, age effects were present in bone tissues of old rats, however no additional dietary effects became visible. Tensile strength of femur and rib did not reveal treatment-related changes. Fourteen days preloading with high dietary magnesium increased plasma magnesium and also skeletal concentrations, although to an only small degree. Nevertheless, time until the appearance of erythema in 50 per cent of the rats subsequently fed the magnesium-deficient diet was significantly delayed.

Aging↗

PubMed1993

High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages.

Expression of the candidate metastasis-suppressor gene nm23-H1 has been shown to correlate inversely with metastatic potential in some human tumors, but not in all. Until now, few studies have been carried out on the activity of the homologous nm23-H2 gene in human cancer. No nm23 transcription studies exist for human lung cancer so far. To determine whether the nm23 genes could have a metastasis-suppressor function in non-small-cell lung carcinoma (NSCLC), pulmonary sarcoma and carcinoids, we analysed both nm23-HI and nm23-H2 mRNA levels in 37 tumor samples obtained from patients who underwent potentially curative resection between 1986 and 1990, and in 4 metastatic tumors obtained from autopsy. As compared to corresponding healthy lung parenchyma, both nm23-HI and nm23-H2 transcript levels were elevated in 37 of 41 tumors. The increases in nm23 mRNA expression were stronger in advanced stages of squamous-cell carcinoma, large-cell carcinoma, sarcoma and carcinoids than in early stages of the respective tumor types. Within stages I and II of squamous-cell carcinoma, significantly higher nm23 mRNA levels were found in poorly differentiated tumors than in moderately differentiated ones. Moreover, an inverse correlation between nm23 expression and disease-free survival of the patients was observed. In conclusion, our results indicate that the increased nm23 expression in the analysed tumors is not consistent with the proposed metastasis-suppressor function, but the 2 nm23 genes nevertheless may be implicated in the mechanism of tumor progression.

Adenocarcinoma↗

PubMed1993

Retrospective analysis of prognostic significance of the estrogen-inducible pS2 gene in male breast carcinoma.

BACKGROUND: The estrogen-inducible pS2 gene, originally isolated from a breast cancer cell line, is correlated with hormone-dependent female breast tumors and its expression is associated with longer overall and disease-free survival. METHODS: The authors have investigated 38 samples of carcinomas of the male breast for pS2 expression by using a monoclonal antibody. The immunostaining was compared with clinical data, in particular, to the progesterone receptor status, to assess a possible prognostic value of this parameter. RESULTS: Although most cases (27 of 38) were immunopositive (i.e., above the 5th percentile of immunoreactive cells), no correlation with tumor grade and survival was notable. CONCLUSIONS: Therefore, on the contrary to the situation in female breast cancer, pS2 activity failed to constitute a new prognostic parameter in male breast carcinomas.

Adult↗

PubMed1993

Genotypic characterization of prostatic carcinomas: a combined cytogenetic, flow cytometry, and in situ DNA hybridization study.

Cytogenetic studies were performed on 36 biopsies obtained from 26 primary prostatic adenocarcinomas. Following histopathological characterization of control sections, the biopsies were investigated using metaphase cytogenetics, DNA flow cytometry, and fluorescence in situ DNA hybridization. In 12 specimens, no carcinoma was found in control sections by histopathological means. In 24 carcinoma biopsies clonal aberrations were detected in 15 specimens. Tetraploidy as sole aberration was detected in five specimens. Loss of the Y chromosome was seen in eight samples. Only one tumor revealed structural abnormalities. Eight samples were found to be normal (46,XY). Remarkably, nonclonal chromosome aberrations, particularly marked chromosome loss, were frequently detected in prostatic carcinomas and premalignant lesions (prostatic intraepithelial neoplasia). In the series of biopsies investigated by means of cytogenetics and flow cytometry, biopsies with aneuploid DNA content were found to be cytogenetically normal. Conversely, the cytogenetically aberrant clones were found to be of diploid DNA content. Evidence of focal intratumoral heterogeneity was revealed by cytogenetics, flow cytometry, and in situ hybridization.

Aged↗

PubMed1993

Bilateral multicentric papillary renal tumors with heteroclonal origin based on tissue-specific karyotype instability.

BACKGROUND: Papillary chromophilic renal tumors were cytogenetically characterized by combined trisomies 7 and 17 along with other numeric chromosome aberrations. They occurred as bilateral multifocal lesions. METHODS: A patient was presented who simultaneously developed bilateral multicentric papillary renal tumors. Tissue specimens from six tumors and tumor-free kidneys were cytogenetically characterized. RESULTS: The tumors showed trisomy of chromosomes 7, 16, and 17 along with various other numeric abnormalities. In normal tissue from both kidneys, a wide variety of clonal and nonclonal numeric and structural chromosome aberrations were found. CONCLUSIONS: The cytogenetic heteroclonality of the tumors strongly favors the assumption that they arose as independent primaries. A tissue-specific karyotype instability may be the basic event of multiple tumorigenesis.

Adenoma↗

PubMed1993

Telomeric associations and loss of telomeric DNA repeats in renal tumors.

In a series of cytogenetically analyzed renal tumors of different histological types (chromophobe carcinoma, clear-cell carcinoma, chromophilic carcinoma, and oncocytoma) and normal renal tissue, the length of the telomeric DNA repeats was assessed using a (TTAGGG)3 oligonucleotide probe. A strong correlation was noted between pronounced telomere shortening and the appearance of telomeric associations of chromosomes. These data suggest an etiologic role of the loss of telomeric DNA repeats in the formation of telomeric associations and a possible involvement of this mechanism in the pathogenesis of chromosome aberrations in human tumors.

Adenocarcinoma↗

PubMed1993

Role of endosonography in the surgical management of non-Hodgkin's lymphoma of the stomach.

Ten patients with primary gastric non-Hodgkin's lymphoma (NHL) were preoperatively assessed by endoscopic ultrasonography (EUS). Tumor infiltration depth and lymph node involvement were assessed using the TNM classification system. EUS was 80% accurate in determining the TL stage and 90% in detecting lymph node metastases (NL stage). Based on the longitudinal tumor extent (antrum to fundus), as assessed by preoperative (n = 10) and additionally, intraoperative EUS (n = 3), partial gastric resection was performed in nine patients and total gastrectomy in one. All resection specimens had tumor-free resection margins (R0 resection rate 100%). These results were compared to those in 23 patients with gastric NHL operated on prior to the introduction of EUS in the hospital who were comparable with respect to tumor location and extent. In comparison with the ten cases where treatment was guided by EUS, the rate of total gastrectomy was higher (65% versus 10%) and the R0 resection rate lower (72% versus 100%) in this group of 23 patients. These results show that EUS may play a crucial role in the pre-surgical staging of gastric NHL.

Adult↗