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G R Rutteman

Publications and source records attributed to G R Rutteman.

At least 55 records · Page 3Linked to original sources
PubMed1993

Clinical and radiographic manifestations of canine malignant histiocytosis.

The results of clinical and radiographic examinations of 15 dogs with confirmed malignant histiocytosis (MH) were reviewed. The most common clinical signs were anorexia (14 dogs), weight loss (13 dogs), lethargy (13 dogs), anaemia (11 dogs), and dyspnoea and/or coughing (8 dogs). Radiographs revealed abnormalities in all dogs, either intrathoracic (pulmonary nodules or consolidation [7 dogs], mediastinal masses [10 dogs], and incidentally pleural effusion [3 dogs]) or abdominal (hepatomegaly [6 dogs] and splenomegaly [2 dogs]), or both. MH occurs relatively frequently in Bernese Mountain dogs. Both clinical and radiographic signs are non-specific, but when they are present in a middle-aged Bernese Mountain dog, MH should be included in the differential diagnosis.

Anemia↗
PubMed1993

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↗
PubMed1993

DNA ploidy and cell kinetic characteristics in canine non-Hodgkin's lymphoma.

Malignant lymphoma in the dog is frequently postulated and used as a therapeutic model for non-Hodgkin's lymphoma (NHL) in humans. In this study DNA ploidy and the cell kinetic characteristics of canine malignant lymphoma were studied by flow cytometric (FCM) nuclear DNA measurements on fresh frozen tumor tissue from 94 dogs with NHL and on material from non-neoplastic lymph nodes from 20 dogs. The results were correlated with histomorphology, immunophenotype and survival. All non-neoplastic tissues were diploid, whereas of the 94 lymphomas 74 were diploid or near-diploid and 20 aneuploid. Of the aneuploid lymphomas, 1 contained a hypoploid cell population. DNA-indices of the aneuploid peaks ranged from 0.87 to 1.21 (mean 1.11). The mean S-phase fraction (8.2%, SD 4.8) was significantly lower in the non-neoplastic tissues than in the lymphomas (11.4%, SD 5.1). A linear correlation was observed between FCM S-phase fractions and bromodeoxyuridine (BrdU) labeling indices (r = 0.78; p < 0.001) determined in paraffin-embedded tissue sections from 18 dogs with NHL after in vivo BrdU labeling. DNA ploidy status did not correlate to the S-phase fraction. There were no differences in S-phase fraction and DNA ploidy between B cell and T cell lymphomas or between different histological classes using the Working Formulation. No correlation was found between S-phase fraction or DNA ploidy and survival in a series of 59 dogs treated with a combination chemotherapy protocol. It is concluded that the frequency of DNA aneuploidy in canine malignant lymphoma is similar to that in human NHL. In contrast to findings in human NHL, however, no relationship was found between DNA ploidy or cell kinetic features and histomorphology or prognosis.

Animals↗
PubMed1992

[Hormones and mammary tumors in the bitch: a review].

Toxicity studies as well as epidemiological studies in veterinary medicine have shown that both ovarian steroids and a large number of synthetic derivatives may promote the formation of mammary tumours in dogs. Abnormalities in pituitary function, particularly in the secretion of growth hormones, have been assumed to be involved in this process. In the present paper the possible role of endogenous and exogenous hormones in the pathogenesis of mammary tumours in bitches is reviewed. The available evidence suggests that steroid hormones may act at an early stage in the development of tumours by stimulating the proliferation of normal epithelium. This results in an increase in the number of susceptible cells. In addition a growth-stimulating action may be exerted upon cells which have undergone partial malignant transformation, but possibly to a lesser extent upon fully malignant cells at a late stage of tumour development. In advanced mammary cancers steroid receptors are frequently absent, which may indicate a more autonomous pattern of growth. It seems justified to conclude that in clinical practice ovariectomy at an early age as a measure to prevent oestrus is to be preferred to progestin treatment with regard to the risk of mammary carcinoma. Still, there is no indication that in dogs, ovariectomy will reduce the risk of metastasis once the animal is presented with a mammary carcinoma. The earlier assumption that overproduction of growth hormone is an important factor in the pathogenesis of spontaneous mammary tumours in the dogs could not be proven. The role of prolactin and of thyroid hormones in this process continues to be uncertain.

Animals↗
PubMed1992

Contraceptive steroids and the mammary gland: is there a hazard?--Insights from animal studies.

The safety of synthetic steroid hormones to be used for contraception in the human female is tested in rats, beagle dogs, and (once marketing starts) in monkeys. Because early studies did not show a mammary tumor stimulating effect in the human, in contrast to findings in the dog, many objections have been raised to the use of the dog for these toxicity studies. It has been claimed that the dog is unique in its sensitivity to the mammary tumor promoting effect of progestins and that this tumorigenic effect results from progestin-induced growth hormone (GH) induction. A thorough review of the literature does not support these claims. Tumor stimulatory effects of progesterone or synthetic progestins can be observed under some conditions in rodents as well as in cats and monkeys. In addition, recent evidence suggests a role for progesterone in mammary tumorigenesis in the human, and contraceptive steroids may also not be completely without risk. While the suggested role for GH in dog mammary tumorigenesis is far from proven, such a role cannot be excluded in the other species. Whether tumor stimulatory effects of sex steroids are based upon induction of proliferation in target cells or upon genotoxic effects or both is not yet certain.

Animals↗
PubMed1992

Thyrotrophin receptors in normal and neoplastic (primary and metastatic) canine thyroid tissue.

Thyrotrophin (TSH) is the conditional growth factor of thyroid epithelial cells. Abnormalities in TSH-receptor binding such as a low receptor number or low binding affinity may be a marker of thyroid carcinoma or metastases, or may exhibit a relationship with the functional variability of such tissues. The dog was used as a model to characterize TSH-receptor binding in normal thyroid tissues, naturally occurring thyroid neoplasms and distant metastases. In normal dog thyroid tissues, specific 125I-labelled TSH binding ranged from 2.7 to 15.5%, and low cross-reactivity with bovine LH (0.023%) was observed. One class of TSH-binding sites was found in eight normal thyroid tissues and 22 thyroid carcinomas; two normal thyroid tissues and one tumour exhibited two classes of binding sites. The concentration of binding sites was lower in the five carcinomas with reduced pertechnetate uptake (0.09 pmol/mg protein) than in the five thyroid neoplasms with increased uptake (0.19 pmol/mg) (P = 0.055). Compared with the original carcinoma tissues, TSH binding revealed a reduced binding affinity in eight out of eleven metastases. Two metastases showed a complete absence of TSH binding, suggesting that they were not dependent on TSH for growth. We conclude that one class of TSH-binding site is predominant in normal dog thyroid tissues and dog thyroid carcinomas. TSH could therefore contribute, at least in theory, to further growth of primary dog thyroid carcinomas. Secondly, assays measuring TSH binding may not be able to discriminate between malignant and benign dog thyroid tumours. TSH receptor number or affinity may be related to the functional variability of thyroid neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Steroid receptors in mammary tumours of the cat.

The capacity of steroidal regulatory influence on benign and malignant mammary tissue in cats was investigated. Estrogen, progestin, and (in some cats) androgen receptor levels in the cytosol were measured by a multiconcentration dextran-coated charcoal method in non-affected mammary tissue (NAMT) and in benign and malignant mammary lesions from 34 cats. Receptor levels less than 5 fmol/mg protein were considered negative. Since 3 out of 4 NAMT samples had low-positive estrogen receptor and progestin receptor levels, we considered specimens in which tumour cells were intermeshed with NAMT separate from "pure" tumour specimens. The variation in estrogen receptor expression between the different tissues was moderate, there being 9/17 malignant lesions (without NAMT) estrogen receptor+ as compared with 6/6 benign lesions (without NAMT) (p less than 0.05). The variation in progestin receptor expression was greater (p less than 0.02), with only 5/17 malignant lesions-(without NAMT) progestin receptor+ as compared with 6/6 benign lesions (without NAMT). The difference in progestin receptor levels between these 2 groups was also statistically significant. In 5 cats metastases were also assayed and 2 had a low-positive estrogen receptor level, whereas 1 had a low-positive progestin receptor level. Two of 9 malignant lesions (without NAMT) had positive androgen receptor levels. Comparison of the steroid receptor expression of human and feline mammary cancer indicates that estrogen receptor and progestin receptor levels are lower in the latter. This may indicate that loss of steroid hormone dependency occurs at an earlier stage of the disease in feline mammary cancer than in human breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Progestins and growth hormone excess in the dog.

Chronic overproduction of growth hormone in man and the cat is most often caused by a GH-producing tumour of the pituitary gland. In dogs the usual cause is quite different. In this species endogenous progestins (during metestrus) and exogenous progestins (used to prevent estrus) cause excessive GH secretion that is reversible. For a better understanding of the mechanism of progestin-induced GH synthesis and secretion, studies were carried out in healthy dogs and in dogs presented with GH excess. The effectiveness of stimulation of GH secretion by hGHRH, and clonidine and of the inhibition with the somatostatin analogue SMS 201-995 were evaluated in healthy male dogs. SMS 201-995 had no influence on basal plasma GH levels, but significantly inhibited the hGHRH and clonidine-evoked GH release. In healthy female dogs the basal concentrations of plasma GH were significantly higher during metestrus than during anestrus. The elevated basal plasma GH levels were associated with a diminished responsiveness to stimulation with clonidine. In female dogs with experimental or spontaneous progestin-induced chronic overproduction of GH (and IGF-I), plasma GH levels were completely unresponsive to stimulation with hGHRH and clonidine and to inhibition with SMS 201-995. It is concluded that in the female dog the progestin-induced GH excess has characteristics of autonomous secretion.

Acromegaly↗
PubMed1990

Flow cytometric DNA ploidy analysis of feline mammary tumors.

Flow cytometric DNA analysis was performed on biopsies from 9 nonmalignant and 111 malignant (primary and metastatic) feline mammary lesions. In our series, 46.3% of the primary mammary carcinomas appeared to be aneuploid, whereas all but one benign breast lesion were diploid. The degree of aneuploidy in carcinomas was low, with a relatively high number of primary tumors (12 of 82) displaying hypodiploidy. Aneuploidy was not found to be correlated with any specific histological tumor type, vascular invasion, tumor size, or histological malignancy grade or with the separate components thereof. Comparison of the ploidy in primary and metastatic tumors from the same cases revealed a remarkable stability, both in time and location of appearance of the metastases. It is concluded that with respect to DNA ploidy feline mammary carcinoma has more in common with canine mammary carcinoma than with human mammary carcinoma. Further prospective studies are necessary to clarify the implications of aneuploidy in feline mammary carcinoma for tumor behavior and prognosis.

Aneuploidy↗
PubMed1990

Immunological aspects of mammary tumors in dogs and cats: a survey including own studies and pertinent literature.

Naturally occurring cancer in companion animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals. In dogs and cats, as in man, a role for immune responses is indicated in the development of tumors. A survey is presented based on the literature and our own studies concerning the immunological and immunotherapeutic aspects of canine and feline mammary neoplasia. In dogs bearing mammary neoplasms, circulating immune complexes appear to play a negative role in the generation of effective antitumor immune responses. The functional role of peripheral blood lymphocytes and tumor-infiltrating lymphocytes in dogs and cats with mammary tumors is not yet fully established. No tumor antigen responsible for humoral or cellular responses has yet been identified. Extracorporeal perfusion of serum of dogs with mammary tumors and subcutaneous administration of mitomycin- and neuraminidase-treated autologous tumor cells are associated with improved prognosis. The opposite was true for i.v. treatment with BCG or Corynebacterium parvum vaccine in our study, in contrast to a previous report. A number of other treatment modalities in cats and dogs with mammary carcinomas failed to induce tumor regression. Canine and feline mammary carcinomas are good candidates for modern immunotherapeutic approaches.

Animals↗
PubMed1990

Polyethylene glycol-L-asparaginase versus native L-asparaginase in canine non-Hodgkin's lymphoma.

42 dogs with non-Hodgkin's lymphoma (NHL) were randomized for treatment with either PEG-L-asparaginase 10 IU/kg intramuscularly (n = 22) or L-asparaginase 400 IU/kg intraperitoneally (n = 20). Another 20 dogs were treated with either PEG-L-asparaginase 30 IU/kg (n = 10) or L-asparaginase 400 IU/kg (n = 10). Each treatment protocol consisted of two asparaginase treatments followed by a 10-week period of induction chemotherapy and then maintenance on asparaginase until progression occurred. No significant differences were found between treatments in the response rates after 2 weeks of asparaginase therapy or in the time to relapse, the time to treatment failure or the remission period. The reaction to asparaginase after the initial 2 weeks was a prognostic factor for the total duration of remission under asparaginase maintenance therapy. No side-effects were noted in the dogs treated with PEG-L-asparaginase, whereas 14 (48%) of the L-asparaginase treated dogs had side-effects related to this drug, including anaphylactic shock (9), anorexia or vomiting (4), hypersensitivity-related oedema (3), seizures (1) and acute pancreatitis (1). No abnormalities in clotting times, fibrinogen levels or antithrombin-III levels were found in any of the 62 dogs. PEG-L-asparaginase has the same anti-tumour activity as native L-asparaginase in dogs with NHL, but lacks side-effects.

Animals↗
PubMed1989

Isolation of autonomously growing dog mammary tumor cell lines cultured in medium supplemented with serum treated to inactivate growth factors.

Conventional methods for isolation of cell lines from carcinomas suffer inherently from a lack of advantage for proliferation of transformed cells as opposed to contaminating fibroblasts and normal epithelial cells. To isolate cell lines from metastases of estrogen receptor-negative mammary carcinomas in dogs, we applied a novel method using medium supplemented with serum treated to inactivate growth factors. Under these conditions, autonomously growing tumor cells are selectively allowed to proliferate. In this way, four autonomously growing tumor cell lines were obtained from metastases of two dogs. Tumors formed from cells implanted in C3H nude mice closely resembled the original dog tumors, indicating that the main result of this selective procedure was suppression of normal cell proliferation. Serum treated to inactivate growth factors seems to be an important medium supplement for isolation of autonomously growing tumor cell lines, which may be valuable tools for future studies on regulation of cell proliferation in advanced hormone-independent mammary tumors.

Animals↗
PubMed1988

Flow cytometric analysis of DNA ploidy in canine mammary tumors.

DNA ploidy has been determined using flow cytometry in 23 nonmalignant and 34 malignant (primary and metastatic) mammary tumors from 46 dogs. This parameter was compared with clinical stage, histology, and estrogen and progesterone receptor analysis. Twenty-one of 34 cancers (61.8%) from 32 dogs were DNA aneuploid. Aneuploidy was also found in 4 of 23 nonmalignant tumors (17.4%) from 20 dogs. Regional lymph nodes were involved in 6 of 10 diploid and 3 of 9 aneuploid cancers of dogs with operable disease. The aneuploidy incidence was higher in dogs that had distant metastasis at initial diagnosis (8 of 11) than in those presented with local or locoregional disease (9 of 19), although this difference was not statistically significant. DNA aneuploidy incidence was not found to be related to histological tumor type, histological malignancy grade, nuclear grade, or steroid receptor presence. Heterogeneity in DNA content was found in 4 of 32 cancers (30 dogs) in samples from primary or locally recurrent lesions. In 3 of 16 cancers that were analyzed both at the primary and at secondary sites of growth, a significant variation in DNA content was observed. The degree of aneuploidy in the dog cancers was much lower than seen for human breast carcinomas with a relatively high frequency of hypoploid stemlines (7 of 34 cancers, 20.6%). The frequency distribution of DNA indices in dog mammary cancers indicates that aneuploidy evolution probably differs from that of human breast cancer.

Animals↗