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N Wernert

Publications and source records attributed to N Wernert.

At least 55 records · Page 3Linked to original sources
PubMed1994

[How tumors abuse their host: the transcription factor c-ets1 and the regulation of tumor angiogenesis or invasion].

During their progression, epithelial tumors induce a stromal reaction essential for their development and for metastasis. In situ hybridization studies have revealed that the protooncogene c-ets1 is expressed in endothelial cells at the beginning tumor angiogenesis, and in stromal fibroblasts surrounding invasive tumors. C-ets1 encodes a transcription factor that may activate the transcription of genes encoding collagenase 1, stromelysin 1 and urokinase plasminogen activator, proteases involved in extracellular matrix degradation. A working hypothesis is that c-Ets1 takes part in regulating invasive processes by controlling the transcription of these genes. Experimental evidences that may confirm this hypothesis will be discussed.

Animals↗
PubMed1994

Does the transcription factor c-ets1 take part in the regulation of angiogenesis and tumor invasion?

The c-ets1 proto-oncogene encodes a transcription factor that binds a GGAA/T purine rich core DNA sequence. During normal as well as pathological development, the expression of c-ets1 is associated with the occurrence of invasive processes, either in invading cells or in the invaded tissue. Cellular regulatory sequences responsive to the c-Ets1 proteins include a urokinase-type plasminogen activator (u-PA) gene enhancer, the stromelysin-1 and the collagenase-1 gene promoters. Since invasive processes are thought to require the remodeling of the extra-cellular matrix, we investigate the relationships between c-Ets1 and the expression pattern of transcripts encoding these matrix degrading proteases, in embryos and in solid tumors.

Neovascularization, Pathologic↗
PubMed1993

Heparin does not inhibit oncogene induction in rabbit aorta following balloon denudation.

OBJECTIVE: Smooth muscle cell proliferation and migration are the predominant responses to intimal and medial injury after percutaneous transluminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that the antiproliferative effect of heparin in vivo may be related to an inhibition of proto-oncogene expression, the effects of pretreatment with heparin on the expression of the c-myc, c-fos and c-jun proto-oncogenes were examined in a rabbit model of balloon denudation. METHODS: Animals were randomised 5 h before balloon denudation to receive a subcutaneous injection of unfractionated heparin (7500 IU.kg-1, n = 7) or saline (n = 6). Total RNA extracted from the aorta 1 h after balloon denudation was analysed by northern blot technique. A histological study was also performed in saline treated (n = 4) and heparin treated (n = 4) animals 28 d after balloon denudation. RESULTS: The histological study showed that the degree of neointimal thickening was significantly less in heparin treated animals. However, the level of expression of the proto-oncogenes we studied was similar in both groups. CONCLUSIONS: Heparin inhibits neointimal thickening after balloon denudation. This inhibition is not associated with an overall decrease in the level of expression of the c-myc, c-fos, or c-jun proto-oncogenes in the arterial wall, suggesting that the antiproliferative effect of heparin may be due to an effect on other events in the cell cycle.

Animals↗
PubMed1993

[Does oncogene c-ets 1 participate in the regulation of tumor angiogenesis?].

The formation of new blood vessels is an essential process in embryonic development and wound healing, for tumor growth and metastasis. In situ hybridization studies have revealed that the protooncogene c-est1 is expressed in endothelial cells at the beginning of blood vessel formation, in normal and pathological conditions. c-ets1 encodes a transcription factor, a protein which binds specifically to DNA and which regulates the transcription of genes containing these specific binding sequences in their promotors. Thus, in vitro experiments suggest that c-ets1 may activate the transcription of genes encoding collagenase 1, stromelysine 1 and urokinase plasminogen activator, proteases involved in extracellular matrix degradation. A working hypothesis is that c-ets1 takes part in regulating angiogenesis by controlling the transcription of these genes whose activity is necessary for the migration of endothelial cells from pre-existing capillaries. This hypothesis is discussed with respect to current experimental evidence and to the complexity of the regulatory network controlling gene transcription and extracellular matrix degradation.

Animals↗
PubMed1992

Distribution of basement membranes in primary and metastatic carcinomas of the prostate.

The presence of periacinar and pericellular basement membranes (BMs) has been reported recently in common prostatic adenocarcinomas. In this study we extended our investigations of BMs on lymph node and hematogenous metastases, primary prostatic cancer with unusual histologic features, and posttreatment tumors. In contrast to prostatic malignancies that derive from the transitional epithelium (squamous cell carcinoma, prostatic transitional cell carcinoma) and prostatic involvement by bladder cancer, inconspicuous stromal changes and distinct BM formations at the site of tumor invasion were observed in carcinomas deriving from the secretory epithelium (papillary ductal carcinoma) and from the basal cell (basal cell carcinoma). Even highly malignant anaplastic and small cell carcinomas, as well as irradiated and/or hormonally treated tumors, showed distinct BM formations in contact with the stroma. The same observations could be made in lymphatic and hematogenous metastases of different anatomic sites. These findings indicate that prostatic malignancies may retain BMs even in high-grade lesions, metastases, posttreatment tumors, and variants of prostatic adenocarcinoma.

Basement Membrane↗
PubMed1992

The 'female prostate': location, morphology, immunohistochemical characteristics and significance.

Using immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we can demonstrate prostate-analogous periurethral glands (the 'female prostate') in 66.7% of 33 cases. Histomorphologically, these glands resemble strongly the male prostate glands before puberty. They remain immature throughout life from the fetal period up to advanced age obviously because of a lack of an androgenic stimulus. The glands have long ducts leading into the urethra. A proper stroma component is missing. The immunohistochemical behavior of these glands also corresponds widely to that of the male prostate glands before puberty. No indications can be found for a proper biological function.

Acid Phosphatase↗
PubMed1992

c-ets1 proto-oncogene is a transcription factor expressed in endothelial cells during tumor vascularization and other forms of angiogenesis in humans.

The c-ets1 proteins are transcriptional activators expressed within endothelial cells during blood vessel development in chick embryos. The authors show by in situ hybridization that c-ets1 is transcribed in the endothelia during angiogenesis in human embryos, in granulation tissue, and especially during tumor vascularization. c-ets1 mRNAs were also detected in the fibrocytes of tumor stroma and in the spindle cells of Kaposi's sarcomas, regarded as cells of endothelial origin. It has been shown that the c-ets proteins activate transcription through a PEA3 motif that plays a role in the stimulation of transcription of urokinase-type plasminogen-activator (u-PA), stromelysin and collagenase genes. The authors demonstrate in vitro that the angiogenic factor TNF alpha increases transiently the amount of both c-ets1 and u-PA mRNA in confluent human umbilical vein endothelial cells. Therefore, the authors suggest that the c-ets1 proteins might regulate the transcription of the genes coding for matrix-degrading proteases, which are necessary for both angiogenesis and tumor invasion.

Adenocarcinoma↗
PubMed1991

Relation of endocrine-paracrine cells to cell proliferation in normal, hyperplastic, and neoplastic human prostate.

The relative distribution pattern of the pan-endocrine marker Chromogranin A (Chr A) and the proliferation-associated Ki-67 antigen was investigated in 20 prospectively sampled prostatectomy specimens. In cryostat sections, the Chr A immunoreactivity showed evidence of endocrine differentiation in all 15 prostatic adenocarcinomas. Nine tumors displayed a weak, 5 a moderate, and 1 adenocarcinoma a strong endocrine differentiation. These findings highlight the importance of endocrine differentiation in prostate malignancy that histologically resembles ordinary adenocarcinomas. The simultaneous demonstration of Ki-67 and Chr A revealed that in normal, hyperplastic, and neoplastic prostate tissue Chr A-positive cells were preferentially situated in proximity to Ki-67-labeled cells. This relative distribution pattern of both markers may indicate that endocrine cells are involved in controlling cell proliferation through a paracrine hormonal mechanism. However, an obvious correlation was not found between the degree of endocrine differentiation and proliferative activity in prostatic adenocarcinomas. Furthermore, a coexpression of Ki-67 and Chr A in the same (tumor) cells was not observed suggesting that the endocrine phenotype is only expressed in the G0 phase of the cell cycle as well as in normal, hyperplastic, and neoplastic conditions.

Adenocarcinoma↗
PubMed1991

Basement membranes in fetal, adult normal, hyperplastic and neoplastic human prostate.

The distribution of the various basement membrane (BM) components (type IV collagen, laminin and heparan sulphate proteoglycan) was studied in fetal, adult normal, hyperplastic and neoplastic prostates in formalin- and ethanol-fixed paraffin-embedded specimens. Stromal, epithelial and neoplastic BMs expressed differential susceptibility to pepsin treatment, suggesting conformational differences in the expression of epitopes on BM proteins in distinct anatomical structures and various lesions of the human prostate. In fetal prostate the acinar BM was regular and continuous in contrast to normal adult prostate and various hyperplastic conditions where the acinar BM was locally thickened or unreactive to the anti-BM antibodies. The localization pattern of BM components in grade I and grade II phases of prostatic cancer did not differ essentially from those found in various hyperplastic lesions. Regardless of the histopathological grade of malignancy, prostatic carcinoma cells were surrounded by distinct pericellular and periacinar membranes which were present even at points of contact with the stroma. This suggests that stroma invasion is invariably associated with neoplastic BM formations. Immunohistochemical evidence of the stromal or epithelial origin of neoplastic BMs could not be found. However, the consistent extracellular distribution of neoplastic BM components in contact with the stroma indicates that the elaboration of BM material requires a stromal influence.

Adenocarcinoma↗
PubMed1991

[Immunohistochemistry of the prostate and prostate carcinomas].

1. The immature multilayered epithelium of the prostate glands and ducts reacts positively throughout the fetal period up to puberty for the following antigens: Acid prostate phosphatase (PAP), the prostate-specific antigen (PSA), keratins demonstrated by the broadly reacting keratin antibody "AE1 + AE3", keratins from stratum corneum, the keratins 7, 8, 18 and 19, binding sites for the peanut agglutinin (PNA) and carcinoembryonic antigen (CEA). The expression of PAP and PSA varies and can in individual cases even be nonexistent. Alpha-1-antichymotrypsin (ACT) is not demonstrable until birth. It is found only focally in two thirds of the cases. The prostate stroma proves positive for vimentin as well as desmin. In the prostate glands, vimentin may occur focally. Squamous cell metaplasias in the fetal prostate show positive for all antikeratin antisera as well as PNA and CEA. The epithelium of the ejaculatory ducts and seminal vesicles proves positive for all keratins investigated. Vimentin as well as PNA-binding sites are found on a general basis. The urothelium of the prostate urethra also contains all keratins and, in addition, PNA and CEA. Endocrine cells, positive for serotonin, are sparse in the prostate glands, in the prostatic ducts and in the urothelium. 2. The onset of the androgen effect during puberty leads very probably to the morphological differentiation of the immature glandular epithelium into the two cell types, basal cell and secretory cylindric epithelium which differ with regard to their immunohistochemical behavior. The glands of benign nodular hyperplasia, including special forms, as well as epithelial alterations with nuclear atypia behave immunohistochemically exactly like normal prostate glands. The markers PAP, PSA, CEA, ACT, the keratins 8 and 18 and focally occurring vimentin are expressed exclusively in the secretory epithelium of the prostate glands and ducts, and not in the basal cells. In contrast, antisera against the following antigens stain only the basal cells and basal cell hyperplasia: Keratins from stratum corneum, a common epitope of the keratins 4, 5 and 6 (antibody KA1) and both the estrogen and progesterone receptor. Squamous cell metaplasias behave immunohistochemically like the basal cells. The keratins 7 and 19, desmoplakin, PNA as well as the patients' own blood group antigens are found in both the basal cells and the secretory epithelium. Keratin 7 and the blood group antigens are always only found focally. PNA-binding sites are secreted by the cylindric epithelium. Atrophic glands and the glands in postatrophic hyperplasia share immunohistochemical features with both the basal cells and the secretory epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1990

Morphological and immunohistochemical investigations of the utriculus prostaticus from the fetal period up to adulthood.

We investigated the utriculus prostaticus from the fetal period up to adulthood in 148 prostates. During the second half of gestation the utriculus had a simple tubular or a cystic form and was lined with metaplastic squamous epithelium which showed immunohistochemical positivity for different keratins, carcinoembryonic antigen, and peanut agglutinin binding sites. After birth, alveolar outgrowths of the utriculus developed. After puberty, the utriculus had become a complicated and variable structure. The epithelium no longer differed from that of the prostate glands either morphologically or immunohistochemically. Within the epithelium numerous endocrine cells were found containing neuron-specific enolase, chromogranin, and serotonin. The utriculus and ejaculatory ducts were embedded in a fibrous stroma with, after birth, numerous plexus-like blood vessels. This fibrous zone was peripherally bordered by a layer of smooth muscle. There was no evidence for a function of the utriculus differing from that of the prostate glands. Since the epithelium of both structures is identical immunohistochemically, the epithelium of the sinus urogenitalis most likely particpates in the lining of the utriculus during embryogenesis.

Adolescent↗
PubMed1990

Squamous cell carcinoma of the prostate.

Eleven case of squamous cell carcinoma of the prostate have been divided into four groups according to their histological features and natural history: a pure squamous cell carcinoma of the prostate (one case); b common prostatic adenocarcinoma with malignant squamous component after oestrogen treatment (two); c urothelial carcinoma of the prostate with malignant squamous cell metaplasia (four); and d urothelial carcinoma of the urinary bladder with squamous cell metaplasia growing into the prostate (four). The squamous portions may spread to invade the fibromuscular stroma and grow in prostatic ducts. Necrosis of comedo type and inflammatory infiltrates appeared in a number of cases. The survival times of nine patients ranged from 1 to 17 months. Squamous components were shown by immunohistochemistry to contain various keratin types, carcino-embryonic antigen and peanut agglutinin binding sites. Whenever a squamous cell carcinoma in the prostate is diagnosed histologically various possibilities as to its origin should be considered.

Aged↗
PubMed1990

Nephrogenic adenoma of the bladder in a child--immunohistochemical and lectinhistochemical investigations.

A morphological study of a 6-year-old girl with a nephrogenic adenoma of the bladder is presented. The tumor developed 4 years after multiple reconstructive operations of the urinary tract. Immuno- and lectinhistochemically, the tubular structure of the lesion resembled that of a collecting tubule. A conservative approach was the treatment of choice in the absence of microscopically malignant changes.

Adenoma↗
PubMed1989

Immunohistochemical analysis of the topographical relationship between the estrogen- and progesterone receptor in five human breast cancers. A simultaneous demonstration of both nuclear receptors in the same section by using a computer-assisted image processing.

A technique is described which allows precise assessment of the topographical relationship between the estrogen receptor (ER) and the progesterone receptor (PR) in the same histological section. It is based on the analysis of the results of immunohistochemical double staining by computer-assisted image processing. Five human ductal breast cancers were examined. The simultaneous demonstration of both receptors consists in the following principal steps: The primary antisera against the ER (monoclonal rat antibody) and the PR (monoclonal mouse antibody) are incubated simultaneously, but only the anti-ER antibody is demonstrated in the first staining step by using a goat anti-rat antibody as the linking antibody and the PAP complex from the rat, both antisera from the ER-ICA kit. The result is stored as a digitized grey image ("1. object image"). Then the colored end product and the residual peroxidase activity of the PAP complex are removed. In the second staining sequence the anti-PR-antibody is demonstrated by using a rabbit anti-mouse antibody as the linking antibody and the PAP complex from the mouse. The result is exactly positioned and also stored as a digitized grey image ("2. object image"). Though antibodies raised in different species were used, cross-reactivity could not be avoided. Grey values generated by cross-reactivity between the different antibody systems are evaluated in negative controls and are eliminated in the object images. The remaining (specifically stained) structures of both object images are copied into a final image so that the topographical relationship of the ER and the PR becomes obvious. The results show that in the five carcinomas investigated three types of receptor-positive tumour cells can be distinguished: Cells which coexpress the ER and the PR (1), cells which express either the ER (2) or the PR (3). The number of tumour cells showing one of these expression patterns varies from tumour to tumour.

Breast Neoplasms↗