Multichromatic phenotyping of HER receptor coexpression in breast tumor tissue samples using flow cytometry--possibilities and limitations.

The prognostic significance of HER2 expression in human breast carcinomas is beyond dispute nowadays. The HER family of receptor tyrosine kinases comprises four members (HER1/ErbB1/EGFR, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4) that act in concert via transactivation and consequently compose a functional signaling unit. Besides HER2 overexpression, coexpression of other HER receptors has substantial impact on course of disease and potential therapeutic benefit.

Presence of HER4 associates with increased sensitivity to Herceptin in patients with metastatic breast cancer.

Introduction: HER2 overexpression, or rather HER2 gene amplification, is indicative for Herceptin therapy in both metastatic and pre-metastatic breast cancer patients. Patient's individual sensitivity to Herceptin treatment, however, varies enormously and spans from effectual responsiveness over acquired insensitivity to complete resistance from the outset. Thus no predictive information can be deduced from HER2 determination so that molecular biomarkers indicative for Herceptin sensitivity or resistance need to be identified.

Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients.

Introduction: The HER (human EGFR related) family of receptor tyrosine kinases (HER1/EGFR (epidermal growth factor receptor)/c-erbB1, HER2/c-erbB2, HER3/c-erbB3 and HER4/c-erbB4) shares a high degree of structural and functional homology. It constitutes a complex network, coupling various extracellular ligands to intracellular signal transduction pathways resulting in receptor interaction and cross-activation. The most famous family member is HER2, which is a target in Herceptin therapy in metastatic status and also in adjuvant therapy of breast cancer in the event of dysregulation as a result of gene amplification and resulting protein overexpression.

Mercuric dichloride induces DNA damage in human salivary gland tissue cells and lymphocytes.

Amalgam is still one of the most frequently used dental filling materials. However, the possible adverse effects especially that of the mercuric component have led to continued controversy. Considering that mercury may be released from amalgam fillings into the oral cavity and also reach the circulating blood after absorption and resorption, it eventually may contribute to tumorigenesis in a variety of target cells.

Cytotoxic and genotoxic effects of resin monomers in human salivary gland tissue and lymphocytes as assessed by the single cell microgel electrophoresis (Comet) assay.

Malignant tumors of the three major pairs and the numerous minor salivary glands in humans are rare, and little is known about their various etiologies. Considering the fact that resin monomers from dental restorative materials are released into the saliva and diffuse into the tooth pulp or gingiva, mucosa, and salivary glands, this may potentially contribute to tumorigenesis. Resin monomers may also be reabsorbed and reach the circulating blood as well.

[Does nicotine add to the carcinogenic strain of tobacco smoke?].

Background: It is accepted that nicotine in tobacco smoke causes addiction via nicotinic acetylcholine receptors in the central nervous system. For a long time, the tumorigenic potential of smoking was attributed to compounds other than nicotine. However, more recently data have accumulated which suggest that nicotine may add to the cancer risk by stimulating cellular growth via non-neuronal acetylcholine receptors, by suppressing apoptosis, and by inducing angiogenesis not only in atheromatous plaques but also in tumors.

Genotoxicity of nicotine in mini-organ cultures of human upper aerodigestive tract epithelia.

The direct role of nicotine in tobacco carcinogenesis is still controversial. Recently, DNA damage by nicotine has been demonstrated in isolated human tonsillar tissue cells. Presently, these effects were investigated using mini-organ cultures (MOC) of human nasal epithelia.

[Mini-organ cultures of human nasal mucosa. A model for eco-genotoxicological investigations].

Background: Volatile and ingestive xenobiotics may induce cancer in the mucosa of the upper aerodigestive tract. A new model is presented combining mini-organ cultures of human mucosa and the Comet assay that allows investigation of tumor initiation steps in vitro.

Method: Specimens of human mucosa of the inferior nasal turbinates were cultured as mini-organs and exposed to xenobiotics once, twice or three times with consecutive repair intervals.

The tobacco alkaloid nicotine demonstrates genotoxicity in human tonsillar tissue and lymphocytes.

Recent studies suggest a direct contribution of nicotine, the addictive component of tobacco and tobacco smoke, to human carcinogenesis. To assess the genotoxicity of nicotine, the DNA-damaging effect on human lymphocytes and target cells from lymphatic tissue of the palatine tonsils from 10 healthy patients was tested with the alkaline single-cell microgel electrophoresis (Comet) assay. The degree of DNA migration, a measure of possible DNA single strand breaks, alkali labile sites, and incomplete excision repair sites, was expressed as the Olive tail moment, the percentage of DNA in the tail, and the tail length.

Mono(2-ethylhexyl)phthalate exhibits genotoxic effects in human lymphocytes and mucosal cells of the upper aerodigestive tract in the comet assay.

Phthalic acid esters such as di(2-ethylhexyl)phthalate (DEHP) are widely used as plasticizers in PVC products manufactured for commercial, medical, and consumer purposes. Humans are exposed to phthalates originating, e.g.

Toxicological assessment of noxious inhalants.

In the past centuries mankind has been exposed to various forms of air pollution not only at his occupational but also in his social environment. He mainly gets exposed with these pollutants through the respiratory organs and partially absorbs them into the body. Many of these airborne substances can be harmful for humans and some of them may account for tumorigenic effects.

Effects of naloxone infusion on plasma levels of LH, FSH, and in addition TSH and prolactin in males, before and after oestrogen or anti-oestrogen treatment.

The inhibitory action of endogenous opioids on gonadotrophin release is now well documented. Since LHRH-producing neurons do not possess oestrogen-receptors, it is likely that some other compound mediates the negative feedback action of oestrogens on the gonadotrophin release in the male. To test the hypothesis that endogenous opioids are implicated in this negative feedback action in the human male, the opioid receptor antagonist naloxone (2 mg/h for 4 h) was infused into 7 normogonadotrophic oligozoospermic men before and after 6 weeks of treatment with the oestrogen-receptor antagonist tamoxifen (TAM) (10 mg twice daily) and 6 eugonadal transsexual males before and after 6 weeks of administration of ethinyloestradiol (EE) (10 micrograms three times a day).

Effects of continuous LHRH infusion on plasma levels of LH and FSH in males, before and after oestrogen or anti-oestrogen treatment.

In order to study the role of oestrogens on gonadotrophin release in the human male, LHRH was administered as an infusion at a constant rate of 0.5 micrograms/minute for 4 hours to 7 normogonadotrophic oligozoospermic men, 6 eugonadal male-to-female transsexuals and 9 eugonadal male volunteers. In agreement with in vitro data a biphasic release pattern of both LH and FSH was observed in eugonadal transsexuals as well as in normogonadotrophic oligozoospermic men.

Detection and spontaneous alteration of lymphocyte antigens on slide smears.

Smears of cell suspensions from murine lymphoid organs were prepared on slides, air dried, and processed for detection of immunoglobulin (Ig) and theta (Thy-1) antigens by the unlabeled antibody peroxidase-antiperoxidase (PAP) technique. Satisfactory results were obtained for both antigens on recently made smears. However, slides kept at room temperature showed a progressive decrease in staining of the two antigens with time.

[Biology, serology and biochemistry of leucemogenic viruses derived from a radiation-induced tumor of C57BL mice].

Two distinct rat propagates of a radiation leukemia virus (RadLV-Rs) from the C57BL mouse respectively induced characteristic leukemogenic effects. These were found to be related with the infection titers of the isolates, but not with either their antigenic specificities or their viral and proviral genome sequences.

Radioimmunoassay determination of two main cross-reacting viral antigens during radiation and Rauscher induced leukemias.

The two main proteins p 30 and gp 70 from the Rauscher leukemia virus (RLV) have been isolated, labeled with 125I and used in radioimmune competition assays to estimate the amount of cross-reacting antigens produced during the evolution of various leukemias. The Rauscher leukemia in Balb/c mice, the radiation induced leukemia (RadLV) in C57Bl mice and two types derived therefrom by serial passages in mice (RadLV-RS) and in rats (RadLV-rat) were studied. Whereas the p 30 from RLV or RadLV (rat) viruses showed complete identity, the cross-reaction of their gp 70 proteins wasonly partial.

Specific precipitation of mouse and rat alpha 2-macroglobulin by immune sera directed against murine leukemia viruses.

Leukemia viruses preparations obtained from plasma of leukemic mice or rats were used to immunize rabbits. By immunoelectrophoresis, these non-absorbed antisera reacted specifically with one single mouse serum alpha 2 globulin which was further identified as alpha 2-macroglobulin by several criteria, including gel chromatography and nitracentrifugation. When mouse plasma derived virions were used as antigen, they gave rise to antibodies cross-reacting completely with the corresponding mouse and guinea pig protein and partially with rat and calf globulin.

Regulation of the neutral phosphatase in Chlamydomonas reinhardi: an immunogenetic study of wild-type and mutant strains.

In Chlamydomonas reinhardi, the activity of the neutral phosphatase considerably increases when the cells are grown in the absence of inorganic phosphate (Pi). A comparative immunological study of cells grown on media containing Pi or not indicated that the neutral phosphatase was synthesized de novo. Ten mutants lacking the neutral phosphatase and distributed among three genetic loci (PD2, PD3, PD24) were investigated for their ability to produce cross-reacting material (CRM) antigenically related to the wild enzyme.

[Genetic control in the mouse].

Spontaneous mutations and environmental variations are responsible for the biological instability of inbred strains of mice. As far as possible, all external factors should be kept constant in a modern animal house. Several techniques to analyse part of the genome are available.