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Biomedical subjects

W Misdorp

Publications and source records attributed to W Misdorp.

102 records · Page 6Linked to original sources

Tumours in calves: comparative aspects.

In this paper, calf neoplasia is discussed in relation to a series of cases comprising (1). spontaneous congenital bovine tumours of fetuses and newborn animals, (2). spontaneous juvenile-type tumours in calves aged 2-12 months, and (3). iatrogenic tumours of calves. The congenital cases (n=14) consisted of tumours of a predominantly mesenchymal and malignant nature (malignant lymphoma, mesothelioma and mixed mesodermal tumour). In the juvenile cases (n=11), malignant lymphoma and sarcoma were the commonest forms. In comparing tumour patterns in calves with those reported in adult cattle, it was apparent that tumours were less common in the former (6 versus 60 per 100000) and that, with the exception of malignant lymphoma, the types of tumour differed. Carcinomas, which were virtually absent in calves, predominated in adults, probably due to the longer exposure of older animals to carcinogenic factors. In comparing tumour patterns in calves with those reported in pigs and children, it was clear that calf cases were mainly sporadic, with the notable exception of malignant lymphoma in twins. In young pigs, however, several types of tumour (some hereditary) were reported on a single farm as multiple cases. In children, tumours occurred more frequently than in calves, and many neoplasms in both children and calves could be regarded as embryonic tumours or hamartomas. Little is known about the pathogenetic pathways of tumours in calves, with the exception of congenital neuro-fibromatosis (hereditary) and possibly of mesotheliomatosis (due to asbestos). Modern methods of analysing chromosomal and gene aberrations may be helpful in clarifying the pathogenesis of congenital tumours.

Age Distribution↗

Feline mammary tumors: a case-control study of hormonal factors.

Feline mammary carcinomas are, like human breast cancers, spontaneous, locally infiltrative and metastasizing tumors. Therefore, this tumor disease in the cat can serve as a pathogenetic and experimental-therapeutic model for the human counterpart. In the cat, as in the woman, little is so far known with certainty about the hormonal background of mammary tumors. In order to elucidate the role of endogenous and exogenous hormonal factors, a case-control study was conducted. Data on age, history of castration, parity and progestogen administration were compared in cats with malignant or benign mammary tumors on one hand, and in a control group on the other. The statistical relative risks and their significance were assessed using conditional logistic regression analysis. In our study there was a tendency for mammary carcinomas to be found in cats that were older than those bearing benign mammary tumors. Ovariectomy was found to protect against mammary carcinomas but not against benign mammary tumors. No association between parity and mammary tumor risk was found. Regular administration of progestogens was associated with an increased risk of both mammary carcinoma and benign mammary tumors. However, this was not true of irregular progestogen administration and, in general, the administration of progestogens was not associated with an earlier appearance of mammary tumors.

Age Factors↗

Anterior pituitary function in female dogs with spontaneous mammary tumors: I. Growth hormone.

It has been hypothesized that growth hormone (GH) plays a major role in the pathogenesis of canine mammary tumor disease. In order to test this hypothesis, plasma GH levels were measured at rest and during dynamic function tests in dogs with benign or malignant proliferative mammary lesions and in control dogs. Both in control dogs and in dogs with benign disease, basal GH levels were found to be elevated during both metestrus and progestin treatment, as compared to anestrus. Dogs with benign or malignant disease did not have higher basal GH levels than control dogs matched for the effect of endogenous or exogenous progestin exposure. The GH response to glucose or thyrotropin releasing hormone (TRH) did not vary significantly with progestin exposure, nor between the 3 groups of animals. The stimulatory effect of clonidine upon GH secretion was reduced in dogs with benign or malignant disease as compared to controls matched for the effect of progestin exposure. These findings indicate that mammary tumor disease in the dog is associated with a disturbance in the regulation of GH release.

Animals↗

Anterior pituitary function in female dogs with mammary tumors: II. Prolactin.

Plasma prolactin (PRL) concentrations at rest and during dynamic tests were measured in dogs with benign or malignant proliferative mammary lesions and in age-matched healthy control dogs. Basal PRL concentrations of dogs with benign or malignant lesions were not found to be elevated in comparisons controlled for the effects of estrous cycle phase or progestin treatment. A statistically non-significant increase of the PRL response to thyrotropin-releasing hormone (TRH) was seen in separate groups of affected dogs as compared to matched controls. A tendency towards a significantly elevated response to TRH appeared in the combined (benign plus malignant disease) group of affected dogs in anestrus (P = 0.05) and in metestrus (P = 0.09). The PRL response to clonidine was very variable and did not differ between the 3 groups of dogs. The bromocriptine-induced suppression of PRL secretion did not vary significantly among the three groups. These results do not indicate an unequivocal association of mammary tumor development and altered PRL secretion. It is only warranted to conclude that in some dogs the occurrence of benign or malignant mammary lesions is associated with hyper-responsiveness of the PRL secretion to stimulation with TRH.

Animals↗

Feline mammary carcinomas as a model for human breast cancer. II. Comparison of in vivo and in vitro adriamycin sensitivity.

Feline mammary carcinomas were tested for their in vitro and in vivo sensitivity to Adriamycin. In vitro, twenty randomly chosen tumor islands were studied to test the effect of concentrations of the drug ranging from 0.25-2.00 micrograms/ml. In vivo, parts of primary tumors left in situ after surgical biopsy were used to assess the response to five i.v. injections of 30 mg/m2 Adriamycin. When comparing the in vitro and in vivo response, the best sensitivity (100%) was obtained using 2.00 micrograms/ml Adriamycin and the best specificity (75%) using 1.00 microgram/ml Adriamycin, both in vitro. Tumors recurring after treatment showed acquired resistance in vitro.

Adenofibroma↗

Prolactin binding in benign and malignant mammary tissue of female dogs.

Prolactin receptor (PRL-R) concentrations were determined in membrane preparations of canine mammary tumours and of non-affected mammary tissues by a radioreceptor-assay using ovine prolactin (oPRL) both for 125I-labelling and for displacement. Receptor levels greater than or equal to 3 fmol/mg membrane protein were considered positive. Histologically non-affected samples of mammary tissue from 6 dogs were PRL-R positive (12-195 fmol/mg protein). These levels were positively correlated with epithelium content (based on surface area in microscopic sections; r = 0.943, P less than 0.02). In tumour samples where pre-existing mammary epithelium (PME) was present (3 non-malignant and 6 malignant tumour samples; PME content 5-10%), the cut-off limit for PRL-R positivity was increased to 50 fmol/mg protein to forestall false positives due to non-affected tissue. If no PME was present the general limit of 3 fmol/mg protein was maintained. All 18 non-malignant tumours showed PRL-R (18-162 fmol/mg protein). The PRL-R levels were positively correlated with levels of oestrogen-(ER; r = 0.735, P less than 0.002) and progesterone receptors (PgR; r = 0.556, P less than 0.02) as measured by a multi-concentration dextran-coated charcoal method. ER and PgR levels were also proportional (r = 0.660, P less than 0.01). In 6 dogs bearing primary cancers with 5-10% PME, 1 out of a total of 6 tumours was PRL-R positive. In 9 dogs bearing primary or locally recurrent cancers without PME, significant PRL-R levels were measured in 2 out of a total of 10 tumours. Three metastatic sites in 2 other dogs were PRL-R positive. In 2 dogs (1 with a PRL-R negative local recurrence) the metastatic lesions were PRL-R negative. Thus 5 dogs of a total of 18, had PRL-R positive mammary cancers (3-377 fmol/mg protein). Unlike in non-malignant lesions the ER, PgR, and PRL-R levels were not related. In mammary cancer the presence of PRL-R was less common (P less than 0.001), and the ultimate levels less high (P less than 0.001) than in non-malignant tumours. In comparative studies using pooled membrane preparations from benign mammary tissues, oPRL was far more effective than canine prolactin (cPRL) in displacing 125I-oPRL; canine growth hormone (cGH) in this respect was ineffective. It is concluded that non-malignant mammary tissue in the dog generally is PRL-R positive; only some mammary cancers retain the PRL receptors.

Animals↗

The occurrence of estrogen and progestin receptors and anti-estrogen binding sites (AEBS) in canine non-Hodgkin's lymphomas.

In the present study the occurrence of estrogen and progestin receptors in the lymphoid tissue of 20 canine non-Hodgkin's Lymphoma patients was investigated. Lesions in all dogs were histologically classified according to criteria used in human patients. No progestin receptors could be demonstrated. Estrogen receptors were found only in the cytosol of two canine lymphomas. Antiestrogen binding sites were present in all 18 cases examined (range 37-356, median 110 fmol/mg protein). No correlation with age, sex or histological classification was found. A pilot study was carried out in five of these dogs that were negative for estrogen receptors and positive for antiestrogen binding sites. These dogs were treated with the antiestrogen tamoxifen (20-30 mg/day) for 2-3 weeks, but the treatment had no apparent effect. It was concluded that if antiestrogens do play a role in the treatment of non-Hodgkin's lymphoma in the dog, it is most likely not by means of antiestrogen binding sites.

Animals↗

Feline mammary carcinomas as a model for human breast cancer. I. Sensitivity of mammary tumor cells in culture to cytostatic drugs. A preliminary investigation of a predictive test.

Feline mammary carcinomas were found to maintain well in short-term cultures. Principally the same types of nuclear DNA frequency distribution histograms were recognized in feline mammary carcinomas as in human mammary carcinomas. However, the more abnormal histograms are less frequent in feline than in human mammary carcinomas. Feline mammary carcinomas appeared, at least in vitro, most sensitive to Doxorubicin and 5-fluorouracil. Preliminary, thymidine incorporation studies indicate both cytotoxic and cytostatic effects of Doxorubicin and 5-FU. Methotrexate was found to stimulate thymidine incorporation.

Animals↗

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE): a randomized clinical trial in dogs with mammary carcinoma.

In this prospective randomized double-blind clinical study the anti-tumour activity of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) was evaluated as an adjuvant immunotherapy in dogs with mammary tumours of the simple carcinoma type. Dogs were randomized after surgery to one of two treatment groups, in which they were treated with either L-MTP-PE (2 mg/m2 i.v.; Ciba Geigy Basel, Switzerland) twice weekly for eight weeks, or with empty liposomes according to the same protocol. The minimal follow-up period was one year. Thirteen dogs were entered in the L-MTP-PE group and fourteen dogs in the placebo control group. Only minor toxicities (fever and shivering during 10-24 hours) were seen in six dogs treated with L-MTP-PE, these being mainly of the smaller breeds. At the time of evaluation seven dogs were still disease free. In the other twenty dogs the disease-free period (DFP) was ended by local recurrences in 16 and by distant metastases in 4. The difference in DFP between dogs treated with L-MTP-PE (median 165 days, range 15-905) and dogs in the placebo group (median 133 days, range 27-659) was not significant. The difference in overall survival between the dogs treated with L-MTP-PE (median 222 days, range 36-905) and those receiving the placebo (median 182 days, range 54-659) was also not significant. It was concluded that liposome-encapsulated MTP-PE was not efficacious in the treatment of dogs with mammary carcinoma.

Acetylmuramyl-Alanyl-Isoglutamine↗