PubMed HealthSearch

Biomedical subjects

W Misdorp

Publications and source records attributed to W Misdorp.

At least 19 recordsLinked to original sources

P53 gene mutations in osteosarcomas in the dog.

Osteosarcomas in 18 dogs were examined for the presence of p53 mutations in exons 4-8 by single strand conformation polymorphism (SSCP) analysis, followed by sequence analysis in tumors demonstrating abnormal bands in the SSCP analysis. P53 mutations were found in four of the primary tumors in 17 dogs. Metastases studied in two of these dogs in which the primary tumor contained only wild type p53 did not contain mutations, nor those of one dog in which the primary tumor was not studied. The alterations that were found included three missense mutations and one 3 bp insertion.

Animals

Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop.

The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells.

Animals

Veterinary cancer epidemiology.

This paper reviews the impact of veterinary cancer epidemiology on veterinary oncology, human oncology, comparative oncology, and on the etiology and pathogenesis of cancer. The detection of clusters of diseased animals has led to the discovery of the infectious, viral-associated nature of malignant lymphoma of cats, poultry, and cattle. Although some viruses (FeLV, BLV) can, under experimental conditions, cross the species barrier, there is thus far no evidence for a zoonotic hazard for the human. The keeping of pet/birds or pigeons was found to be associated with an increased risk of lung cancer in the bird keepers. Dogs appear to be useful 'sentinels' for environmental hazards (asbestos, dyes, passive smoking, insecticides). The complex pathogenesis of cancer was dissected in an epidemiologic-experimental study in cows, which had intestinal papillomas and carcinomas. Endogenous genetic factors may also play a role in pathogenesis, as is evidenced by species, breed (Boxer!), and family related aggregates of tumour diseases. Epidemiology may provide a means to prevent tumour diseases by, for example, withdrawal of hormones (mammary cancer) or isolation of tumour-virus positive animals (malignant lymphoma).

Animals

[DNA ploidy].

Explore the source record for details and available documents.

Animals

DNA flow cytometry of canine mammary tumours: the relationship of DNA ploidy and S-phase fraction to clinical and histological features.

The DNA ploidy status and S-phase fraction (SPF) of benign proliferative lesions (BPL) and malignant tumours (MT) in the mammary glands of dogs were determined by flow cytometric analysis and the results were related to their clinical and histological features. Seven (14.3 per cent) of 49 BPL and 16 (48.5 per cent) of 33 primary MT had aneuploid G0,1 peaks (P < 0.001). Hypodiploid G0,1 peaks were found in one BPL and in five primary MT. The DNA ploidy status of primary MT was not found to be associated with their size, nodal status, grade of histological malignancy or nuclear grade. In several cases there was intra-tumour heterogeneity in ploidy status independent of histological heterogeneity. The SPF was significantly higher in 27 primary MT than in 45 BPL when diploid and aneploid cases were combined for comparison (P < 0.05), but not when only diploid cases were compared. Among the primary MT the SPF was higher in aneuploid than in diploid tumours (P < 0.05) and it was higher in five MT from five dogs with regional disease than in 22 MT from 19 dogs with local disease (P < 0.05). The SPF was positively correlated with the grade of histological malignancy (P < 0.05) but not with nuclear grade.

Animals

Expression of the gene encoding growth hormone in the human mammary gland.

Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer.

Adolescent

[Differential diagnosis of non-healing 'fungal'patches in horses].

Dermatophytosis is the most common equine skin disease. Mycotic-like lesions that do not disappear are suspected of being sarcoids. The clinical symptoms and therapeutic interventions for both affections are discussed. A short review of the differential diagnoses is presented.

Animals

[Oncology, pathology and companion animal practice].

A review of research in veterinary oncology, as executed in Amsterdam and Utrecht, is presented. Also an inquiry into the cooperation between oncologist, pathologist and practitioner is discussed. It is concluded that microscopic tumour diagnosis is practized at too low a scale (+/- 30%). Veterinary oncology has significance both from the veterinary and the comparative (model) point of view. Etiologic-pathogenetic and biologic-therapeutic aspects are studied in a multidisciplinary way. Intercellular communication, growth factors and intercellular matrix are items of present and future research. Molecular-genetic research is in progress. Prevention of mammary tumours by ovariectomy (dog, cat) and of malignant lymphoma (cat) by fighting FeLV seems promising.

Animals

Expression of epidermal growth factor receptor (EGFR) in non-affected and tumorous mammary tissue of female dogs.

Epidermal growth factor (EGFR), oestrogen (ER), and progestin (PR) receptor concentrations were determined by radioligand binding assay in non-affected mammary tissues (n = 13) and benign (n = 11) and primary/locally recurrent malignant proliferative mammary lesions (n = 45) and metastases (n = 19) in 65 female dogs. The number of specimens expressing EGFR was not significantly different among these tissues, but EGFR concentration was lower in metastases (P = 0.02) than in benign or primary/locally recurrent malignant lesions not mixed with non-affected mammary tissue. The presence of non-affected mammary tissue in primary cancer specimens was noticed as a factor that may influence results of receptor measurements. No relation was found between the expression of EGFR and that of ER or PR in non-affected or in tumorous mammary tissues. It was concluded that in the dog mammary gland EGFR expression is not associated with conditions of steroid receptor absence of biological agressiveness of neoplastic growth.

Animals

Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle actin monoclonal antibodies in canine mammary gland: benign mammary tumours and duct ectasias.

Duct ectasias (n = 2) and different types of benign canine mammary tumours (n = 19) were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In the duct ectasias and in most tumours the epithelial structures revealed an inner and outer cell layer. The inner cell layer was characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K 10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and 17, and a-smooth muscle actin MoAbs. The labelling patterns of both duct ectasias and tumours corresponded largely to the patterns observed in normal mammary gland tissue, although a more distinct heterogeneity was seen. Tumours histomorphologically assumed to be of a myoepithelial origin did not show immunohistochemical features of myoepithelial cells. The myoepithelial nature of the vast majority of spindle-shaped cells present in the adenomas of the complex type and in the fibroadenomas of the benign mixed type could not be confirmed immunohistochemically. These cells, however, unequivocally expressed vimentin, suggesting proliferation of stromal cells in these tumours, which in the fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage. In the duct ectasias and in some tumours, a fraction of elongated stromal cells, probably representing myofibroblasts, was labelled with the alpha-smooth muscle actin MoAb.

Actins

Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle actin monoclonal antibodies in canine mammary gland: malignant mammary tumours.

Ten malignant canine mammary gland tumours and five metastases from three of these tumours were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against different human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In all tumours the neoplastic epithelium was rather homogeneously labelled with the keratin MoAbs RCK 102 (K 5 and 8) and CAM 5.2 (K 8). The adenocarcinomas (n = 5), the solid carcinomas (n = 2), and the carcinosarcoma (n = 1) showed heterogeneous labelling with the MoAbs specific for luminal cell antigens in the normal canine mammary gland, i.e., K 18, K 7 and K 19 MoAbs. These cells were also immunoreactive with K 4 and K 10 MoAbs. The spindle cell carcinomas (n = 2), however, did not react with these MoAbs. All tumours except one adenocarcinoma were characterized by the absence of immunoreactive labelling with the alpha-smooth muscle actin MoAb. In the solid carcinomas this was associated with the absence of labelling with one or both basal cell specific keratin MoAbs, i.e., 8.7 (K 14 and 17) and RCK 107 (K 14), respectively. In contrast, the other malignant tumours showed marked labelling of neoplastic epithelium with these MoAbs. Another remarkable finding was the labelling of a limited to moderate number of neoplastic epithelial cells with the vimentin MoAb. The presence of such labelling patterns in canine mammary gland tumours may be indicative of malignancy. Metastatic tumour tissues had a labelling pattern largely similar to that of the primary tumour, although also loss of reactivity for some keratin MoAbs was seen.

Actins

Immunohistochemistry with keratin, vimentin, desmin, and alpha-smooth muscle actin monoclonal antibodies in canine mammary gland: normal mammary tissue.

Normal canine mammary gland tissue was studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types, vimentin, desmin, and alpha-smooth muscle actin. Both ductal and alveolar luminal cells were immunoreactive with MoAbs recognizing respectively human keratins no. 7, 8, 18 and 19. In addition, some ductal luminal cells were labelled with a keratin 4 and a keratin 10 MoAb. Basal/myoepithelial cells were immunoreactive only with MoAbs directed against keratin 14, keratins 14 and 17, and alpha-smooth muscle actin. The vimentin MoAb merely labelled solitary loose intraluminal cells representing macro-phages or sloughed epithelial cells. These findings correspond largely to observations made in human breast tissue.

Actins

Cytokeratins as markers of initial stages of squamous metaplasia in feline mammary carcinomas.

Expression of keratins (cytokeratins, CK) known to be suitable markers for different types of epithelial differentiation was analyzed in specimens of feline mammary tissue. A panel of specific anti-CK monoclonal antibodies (MAb) was used to determine CK distribution pattern in normal feline tissues (n = 3), and in benign (n = 18) and malignant (n = 20) feline mammary tumors. In selected tumors, the CK distribution pattern was also determined by biochemical methods. A MAb specific for alpha-smooth muscle actin was used to discriminate between myoepithelial cells and luminal epithelial cells. In normal mammary gland tissues, 6 MAb reacted exclusively, either with myoepithelial cells or with luminal epithelial cells. Luminal epithelial cells reacted with MAb specific for CK typical of simple epithelia, whereas myoepithelial cells reacted with MAb specific for CK in basal cells of stratified epithelia. A similar distribution of CK was detected in specimens from benign tumors, except that CK4 was not detected in normal mammary gland tissues and was detected in some ducts in specimens with adenosis. Almost all tumor cells in specimens from malignant tumors reacted with MAb specific for CK typical of simple epithelia. Concomitant expression of CK typical of stratified epithelia was detected in small or large subpopulations of tumor cells in 70% of carcinomas. Cytokeratins typical of basal cell layers and typical for suprabasal layers of inner stratified epithelia were detected. Cytokeratins typical of stratified epithelia were always found in areas of squamous metaplasia, but also were found in adenocarcinomal cells surrounding these areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenofibroma

Hormonal background of canine and feline mammary tumours.

Ovarian steroid hormones and their synthetic derivatives may enhance mammary tumorigenesis in dogs and cats. In toxicity studies of synthetic progestagens a dose-related effect has been observed in the dog, with low-dose exposure sometimes being protective against mammary tumour development. There is some evidence that steroid dependence, as reflected by the presence of steroid receptors (that are nearly always present in normal mammary tissue and benign mammary tumours), is decreased in advanced stages of malignant disease, both in the dog and cat. However, this difference in steroid receptor expression between benign and malignant conditions is not related to any significant alterations in the concentration of receptors for epidermal growth factor. Progestagens have been suggested to promote mammary tumorigenesis in the dog by their induction of growth hormone overproduction; however, there is no conclusive evidence that this effect is necessary for mammary tumour induction. Basal levels of growth hormone and of prolactin were found to be similar in tumour-bearing dogs and age-matched controls.

Animals

[The significance of ovariectomy and progestagens in the development of mammary carcinoma in cats].

Mammary carcinoma in the cat has a poor prognosis. Because of metastasis and local malignity, these tumours are of relevance not only to veterinary practice but also to comparative research as a model to study possible therapies and the aetiology and pathogenesis of the disease. Little is known about the development of mammary tumours in humans and companion animals. A case-control study was carried out to learn more about the role of endogenous and exogenous sex hormones. In the cat, ovariectomy (RR 0.36) had a clear protective effect against the development of mammary carcinoma, whereas regular administration of progestogens clearly increased the risk of carcinoma development (RR 2.81). Our results show that with regard to the evidence of mammary carcinoma, oestrus prevention by ovariectomy is to preferred to the administration of progestogens.

Age Factors

Malignant fibrous histiocytomas in dogs and cats: an immunohistochemical study.

Immunohistochemical staining was performed on seven canine and 10 feline soft tissue tumours histologically diagnosed as malignant fibrous histiocytomas (MFHs) or MFH-like tumours, and eight other histologically specified tumours (non-MFH). This was done to determine if commercially available antibodies that are used routinely in human diagnostic pathology for MFHs would express the same immunohistochemical patterns in canine and feline MFHs and MFH-like tumours. The antibodies were directed against human alpha 1-anti-trypsin (AT), human alpha 1-anti-chymotrypsin (ACT), human lysozyme, bovine S-100 protein and human desmin. AT did not show any immunoreactivity in the tissues investigated. Except for one MFH, all canine MFHs and other soft tissue tumours with a 'histiocytic' character stained for lysozyme and not for S-100. Six out of seven canine MFHs and MFH-like tumours stained positive for desmin as did most non-MFH sarcomas. Most of the canine and feline MFHs and MFH-like tumours were positive for ACT. These findings for ACT staining in canine and feline MFHs and MFH-like tumours are in agreement with the findings in human MFHs. The immunohistochemical results of canine MFHs and MFH-like tumours were different from those in cats. Feline MFHs differed from canine MFHs for both lysozyme and desmin staining.

Animals