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Biomedical subjects

W Misdorp

Publications and source records attributed to W Misdorp.

At least 55 records · Page 3Linked to original sources

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↗

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↗

Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study.

Five cows bearing bovine ocular squamous cell carcinoma (BOSCC) were treated with low doses of recombinant human interleukin-2 (rhIL-2). A dose of 2500 U rhIL-2 was injected intralesionally and another 2500 U were injected into the subparotid regional lymph node once a day during a period of 5 consecutive days. This cycle of 5 days was repeated after an interval of 2 days. Total regression of the tumor was observed in three out of five animals. One cow showed tumor regression (greater than 80%) accompanied by metastases to the regional lymph node that were observed from the fifth week after the beginning of the treatment. Growth of the tumor of the fifth animal was retarded after treatment. In vitro proliferation of peripheral blood lymphocytes was investigated in two animals and tumor-infiltrating lymphocytes in one animal during incubation in various rhIL-2 concentrations. Cytotoxic activity of both cell populations against P815, Yac-1 and BOSCC-derived cell lines increased during incubation with rhIL-2. Cultured BOSCC-infiltrating lymphocytes showed predominant killing of the BOSCC-derived autologous cell line after 4 weeks of culture. Preliminary phenotype analysis did not give conclusive results with respect to the types of cells responsible for killing.

Animals↗

Keratin staining of canine epithelial tissues by a polyclonal antiserum.

The keratin distribution pattern in various canine epithelial tissues has been studied using a commercially available rabbit antiserum, raised against human skin keratins, in an immunoperoxidase staining method with the peroxidase-antiperoxidase complex (PAP). The staining results of two fixation methods were compared. Paraffin sections after fixation in Carnoy's solution showed optimal results, whereas paraffin sections after fixation in 10% buffered formalin resulted in a strongly reduced keratin staining reaction. Keratinizing and non-keratinizing stratified epithelial showed a strong staining reaction. Glandular epithelium and the non-stratified epithelia of internal organs e.g. liver, kidney and intestine did not react with the antiserum. However, glandular ductal epithelium, myoepithelial cells and basal cells in various epithelial tissues showed a positive staining reaction. The results indicate the presence of different keratin types in these canine epithelial tissues. The keratin distribution pattern is compared with the distribution pattern observed in tissues of other species.

Animals↗

An immunohistochemical study of canine tissues with vimentin, desmin, glial fibrillary acidic protein, and neurofilament antisera.

In a wide range of canine tissues the immunoreactivity with commercially available antisera against intermediate filament antigens viz. vimentin, desmin, glial fibrillary acidic protein (GFAP) and neurofilament proteins, was studied. In addition, the results of formalin and Carnoy fixation were compared. Carnoy fixation appeared to result in optimal reactivity for all antisera. Epithelial cells did not react with any of the antisera, with exception of ovarian surface epithelium, which showed staining with the vimentin and desmin antisera. The vimentin antiserum induced staining of several cell types viz. fibroblasts, endothelial cells, chondrocytes, Schwann cells, ependymal cells, astrocytes, Leydig cells, synovial cells, podocytes and some parietal cells of Bowman's capsule. Sertoli cells showed a faint staining reaction. Muscle cells in various tissues reacted with the desmin antiserum. In the kidney a varying number of parietal cells appeared to react as did a restricted number of epithelial cells of proximal tubules and loops of Henle. GFAP reactivity was confined to glial cells, predominantly fibrous astrocytes, Schwann cells and axons. Additionally, some neuronal cell bodies in peripheral ganglia showed staining of varying intensity. Neurofilament staining was restricted to axons and some neurons. The immunoreactivity of canine tissues with these antisera is compared to findings in other species. The results confirm a broad interspecies cross-reactivity of these antisera. They can be used in studying the nature of canine tissues.

Animals↗

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↗

[Chemotherapy of tumors in dogs].

The general principles of chemotherapy in oncology and the various types of antineoplastic drugs are discussed. Particular attention was paid to the results of chemotherapy in dogs and cats as reported in the literature. Chemotherapy is indicated in neoplastic disease characterised by early metastasis and/or local invasive growth. The results of chemotherapy in dogs and cats are so far moderate. Chemotherapy studies in the Netherlands are discussed: predictive in vitro, PEG-asparaginase studies in canine lymphosarcoma and regional perfusion in canine osteosarcoma.

Animals↗

An analysis of spontaneous and chemotherapy-associated changes in skeletal osteosarcomas.

Microscopically assessed changes observed in large sections of osteosarcomas from patients who had undergone pre-operative chemotherapy (PCT) (n = 22), or no chemotherapy (n = 22), were examined either quantitatively, semiquantitatively, or qualitatively. Eight tumour characteristics were associated with the treatment mode by way of a stepwise logistic analysis. Minimal amount of viable tumour tissue (less than 10 per cent) and strong fibroblastic proliferation were each proved to be associated with PCT. These two variables in combination indicated a good response to PCT. The discrimination between PCT and non-PCT patients based on statistical analysis was superior to discrimination based on 'overall impression'.

Adolescent↗

Oestrogen (ER) and progestin receptors (PR) in mammary tissue of the female dog: different receptor profile in non-malignant and malignant states.

Oestrogen (ER) and progestin receptors (PR) were measured in cytosols from histologically normal mammary tissues (n = 30), and in benign (n = 59) and malignant mammary lesions (n = 49) from female dogs. Receptor levels greater than or equal to 5 fmol mg-1 protein were considered positive. The presence of histologically normal mammary epithelium within specimens of primary tumours was noticed as a factor that may cause false-positive receptor results. Receptor levels in non-malignant tissues, and the receptor status of primary cancers did not vary significantly with regard to the phase of oestrous cycle (anoestrus/metoestrus) or the influence of exogenous progestins. ER- or PR-positivity was more frequent and levels of both receptors were higher in 'normal' tissues and in benign lesions than in primary cancers (P less than 0.001). ER and PR levels were higher in benign lesions of dogs also developing malignant mammary tumours than in benign lesions of dogs that did not (P less than 0.02 and P less than 0.05, respectively). Regional and distant cancer metastases were frequently receptor-negative. In some dogs heterogeneity of receptor status was found between different sites of the same cancer. These findings indicate that in non-malignant mammary tissues of adult female dogs expression of the genes encoding ER and PR is common. In malignant tumours this property may become lost, in particular in advanced states of disease.

Animals↗

Canine mammary tumours: protective effect of late ovariectomy and stimulating effect of progestins.

Ovariectomy, even when performed at an advanced age, was found to be to some extent protective against mammary tumour development in dogs. Bitches treated with progestins had a slightly higher risk for mammary tumours (all types, benign and malignant) than controls. Progestin treatment did not increase the risk of mammary cancer. Benign tumours in (treated and untreated) dogs appeared earlier than malignant ones. Progestin treatment resulted in earlier appearance of both benign and malignant tumours than in controls. The ratio solitary/multiple mammary tumours was not significantly different between treated and untreated dogs.

Age Factors↗

[Regional isolation perfusion with cisplatinum in dogs with osteosarcoma of an extremity].

In the treatment of osteosarcoma, it is possible to differentiate between systemic therapy and local regional treatment. Systemic treatment of human patients with osteosarcomas consists in adjuvant chemotherapy. This has considerably improved the prognosis in these cases. The primary object in local regional treatment is to prevent local recurrences and to preserve function. As regards extremities, the aim is to preserve the limbs. In the present investigations, the value of regional chemotherapy by isolated regional perfusion with cis-platinum to dogs is studied. This approach was based on the hypothesis that considerable necrosis of tumours may be produced after perfusion with cis-platinum, thus making extremity-saving surgery possible. Isolated regional perfusion with cis-platinum (30 mg/litre of extremity volume) was performed in nine dogs with osteosarcomas of an extremity. A marked effect on the tumour was detectable on the basis of clinical, radiological and histological parameters. In the opinion of the present authors, regional perfusion with cis-platinum may contribute to extremity-saving treatment of osteosarcomas in dogs and human subjects. However, further studies will be required in order to achieve more adequate quantitation an improvement of local effects. In view of the synergy with cis-platinum, the latter may possibly be attained by the addition of hyperthermia (temperatures above 41.5 degrees C).

Animals↗

Incomplete surgery, local immunostimulation, and recurrence of some tumour types in dogs and cats.

Histologically confirmed inadequate treatment resulted in a lower than expected recurrence percentage in dogs with haemangiopericytoma (38%) and mastocytoma (30%). Clinical suspicion of inadequate tumour treatment did not always correlate with the histologically assessed inadequacy, nor with the appearance of local recurrence. Local recurrence did not seem to be correlated with histological grade of malignancy and tumour size. Local injection of C. parvum vaccine did not result in a lower percentage of local recurrence or longer recurrence-free intervals in any of the three tumour groups (canine haemangiopericytoma, canine mastocytoma, feline mammary carcinoma). Nor was palliative local adjuvant injection of Cp successful in dogs and cats with soft tissue sarcomas or in dogs with gingival melanoma. Re-operation of locally recurrent tumour was successful in some dogs with haemangiopericytoma, in a few with mastocytoma, but not in cats with mammary carcinoma. A trend toward histological progression of recurrences and metastases, when compared with the primary tumours, was not evident. The possible reasons for the relatively low recurrence rate of some tumour types and for the failure of Cp-treatment are discussed.

Adjuvants, Immunologic↗

Immune reactivity in cattle with ocular squamous cell carcinoma after intralesional BCG immunotherapy.

Lymphocyte stimulation with Con A and specific immune reactivity to BCG (antibody formation to BCG and DTH reaction to PPD) were determined in BCG-treated, surgically treated and untreated cows with ocular squamous cell carcinoma. In tumor-bearing cows the Con A-induced proliferation of lymphocytes was reduced when compared to healthy controls. This suppression consisted of a reduced blastogenic response to Con A of lymphocytes from tumor-bearing cows, and the presence of a factor in the sera of these animals, as these sera suppressed the blastogenic response of lymphocytes from healthy cows. BCG had only a minor influence on the suppressive activity. Antibodies to BCG were demonstrated in 50% of the BCG-treated animals. The formation of antibodies was not influenced by intradermal injection of PPD of Mycobacterium bovis. Absorption of a BCG antibody containing serum with BOSCC tumor extracts did not reveal the existence of cross reacting antigens between BCG and BOSCC. Pretherapeutic and posttherapeutic Con A reactivity could not be correlated with clinical response. Of the 30 BCG treated cows 29 developed a positive DTH reaction to PPD. Correlation between clinical response and immune reactivity was seen only with regard to the DTH reaction to PPD: this reaction remained positive for a longer period after treatment in animals with a favorable clinical outcome than in nonresponding animals.

Animals↗

Equine sarcoid: BCG immunotherapy compared to cryosurgery in a prospective randomised clinical trial.

A total of 30 horses with single or multiple sarcoid tumors of the skin were randomly divided into three treatment groups: (i) cryosurgical treatment, (ii) intralesional immunotherapy with a live BCG vaccine, (iii) intralesional immunotherapy with a BCG cell wall preparation. Complete tumour regression was obtained in all 10 cryosurgically treated horses, in 6 of 10 live BCG treated horses, and in 7 of 10 BCG cell wall treated horses. One live BCG and 2 BCG cell wall treated horses showed partial tumour regression of more than 50% of the tumour area. Eleven horses with sarcoid tumours were not eligible for random allocation in the trial because unfavourable site or size of the tumour precluded cryosurgical treatment. These animals were treated with BCG cell wall vaccine except for 1 animal, which was treated with live BCG. In 4 cases this treatment was combined with cytoreductive surgery of the tumour. In this prognostically unfavourable group 8 animals showed complete tumour regression and 3 animals did not respond. Regression after BCG immunotherapy appeared to correlate with size (larger tumours worse response) and localization of the sarcoid (less favourable results in the limb), and increase in peripheral blood leucocytes after the first injection. Horses with a positive delayed type hypersensitivity reaction to PPD before the start of treatment showed a tendency to more favourable prognosis than PPD negative horses. No correlation was present between regression and single or multiple presence of sarcoids, increase in body temperature after injection of BCG and the formation of specific antibodies to BCG. None of the cured animals have shown tumour recurrence 3 to 40 months following treatment.

Animals↗

Clinico-pathological aspects of immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma.

Bovine ocular squamous cell carcinoma (BOSCC) of clinical stage I, mostly situated in the third eyelid, was chosen as a therapy model for squamous cell carcinoma of the head and neck in humans. Block resection was found to be the best method of treatment. Regression was noticed in 19 out of 30 cows treated intratumourously with a single injection of live BCG or BCG cell wall vaccine, followed by recurrence in 8 cases. In 2 untreated cows, complete lasting regression occurred. Regression was significantly more frequently encountered in intratumourously treated cows than in controls. Regression was associated with a high mitotic index, severe infiltrating growth and small amounts of cellular (lymphoid) infiltration. Metastasis was found in 14 out of 50 cows: 5 in 10 untreated controls, 8 in 30 BCG treated cows and 1 in 10 surgically treated cows. The growth rate of progressively growing untreated and of some treated tumours was not associated with the mitotic index nor with other morphological characteristics tested. The mitotic index was found to be higher in the deep infiltrating layer than in the superficial layer of the primary tumour, suggesting that a single biopsy is not sufficiently representative for cell kinetic studies.

Animals↗

[Cancer in dogs and cats. III. General aspects of therapy].

Factors influencing the choice of a particularly therapy of malignant disease in dogs and cats are separately discussed and reviewed in conjunction with each other. The form and stage of malignant disease, the condition of the patient, the attitude of the owner and that of the veterinarian, the availability and risks of tumour therapy and the organization of veterinary health care are briefly discussed. Increase co-operation, national and international, by various disciplines of veterinary science, is essential in improving the treatment of cancer in small animals.

Animals↗

Intratumoral BCG and Corynebacterium parvum therapy of canine mammary tumours before radical mastectomy.

In two parallel studies, bitches with mammary tumour received single intralesional injections of BCG (1 mg: 10(7) living bacteria) and Corybacterium parvum (10(9) killed bacteria) (53 bitches) or C. parvum alone (129 bitches) at the same dosage. Control groups received injections, following the same protocol, of 1 ml BCG suspension medium diluted in saline in the first study (51 bitches) or no injections at all (120 bitches in the second study). A block dissection, including mammary tumours, adjacent mammary glands, and regional lymph nodes, was performed 2 weeks later in all animals. On the basis of histologically confirmed malignant tumours, 48 bitches (25 treated by-immunotherapy and 23 controls) in the first study and 67 bitches (30 treated by immunotherapy and 37 controls) in the second study remained for postsurgical follow-up. The clinical tolerance of the treatment was generally good. No significant differences were found in cumulative survival rates between treated and control group in either studies.

Age Factors↗