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Biomedical subjects

T Smink

Publications and source records attributed to T Smink.

17 recordsLinked to original sources
PubMed1986

A rat lung cancer model based on intrapulmonary implantation of tumour material.

A lung cancer model based on implantation of tumour fragments in the posterior lobe of the right lung of WAG/Rij rats by a surgical procedure has been developed. Two transplantable squamous cell carcinomas which were induced by implanted iridium-192 wires in the lung, were used in this study. The characteristics of these tumours following intrapulmonary implantation are reported with respect to growth rate, invasiveness and metastasizing capacity. The tumour volumes are determined by X-ray chest radiographs. Mean tumour volume doubling times are about 9 days. This system provides a means to evaluate treatment regimens involving irradiation and chemotherapeutic drugs.

Animals↗
PubMed1986

Enhanced success rate of transplantation with human tumors in cyclophosphamide-treated nude mice.

Immunosuppression was investigated to enhance the take rate of various human tumor types in nude BALB/c or B10.LP/Cpb mice. Cyclophosphamide (CY), known as an immunosuppressive agent, was injected ip at a dose of 100 mg/kg 24 hours prior to subcutaneous implantation of tumor fragments obtained from established xenograft lines or from patients. In 3 out of 8 ovarian adenocarcinoma tumor lines, with a take of 50% or less in untreated control animals, tumor take was significantly increased by CY treatment to values between 75 and 100%. No effect of CY treatment on tumor take was seen with squamous cell carcinomas of the head and neck region and with lung and prostatic carcinomas. The growth rate of these xenografts was not affected by CY pretreatment. These results indicate that immunologic mechanisms indeed can play a role in the inhibition of tumor growth in nude mice. CY pretreatment may enhance the success rate of transplantation, but this effect appears to be limited to certain tumors.

Adenocarcinoma↗
PubMed1985

Tumor dependent growth kinetics of human tumor xenografts using the subrenal capsule assay.

Using the subrenal capsule assay modified by us in order to decrease the ingrowth of host cells, evaluation of the growth kinetics of three human ovarian tumors and one human lung tumor were made by multiple measurements of the tumor implantation site over the 6-day growth period. For all tumors, a lag period of 2-3 days was noticed before growth occurred in the subrenal location. In general, estimation of the composition of the fragments growing under the renal capsule did not change greatly in terms of percentage tumor of which they consisted but by day 6 most had shown a significant degree of host cell infiltration despite the effects of pre-implantation immunosuppression. We would suggest that only certain human tumors are suitable for implantation using this technique. Further, it appears that within even this group of selected tumors only some are suitable for drug studies, those having established exponential growth early enough so that a measurable endpoint can be reached within the 6-day time limit of the assay.

Animals↗
PubMed1984

Improvements and limitations of the subrenal capsule assay for determining tumour sensitivity to cytostatic drugs.

Cyclophosphamide (CY) prevented the host response from occurring in treated animals, and we therefore evaluated CY and other immunosuppressive forms of pretreatment in normal mice using the subrenal capsule assay initially for transplanted and later also for primary tumours. CY pretreatment, 4 or 4.5 Gy whole-body irradiation and cortisone were superior to silica in reducing host cell infiltration, and irradiation as pretreatment has become our routine technique. The addition of cortisone acetate to irradiation was of minor benefit in only 1/3 transplanted lines. When primary tumours were tested, the irradiation was only rarely able to completely prevent cellular infiltration. Only 7/11 ovarian tumours and 3/9 lung tumours were evaluable as tumour specimens (greater than 50% tumour) in preirradiated mice. The degree of infiltration and fibrosis was similar in transplants in irradiated normal mice or in athymic nude mice, suggesting that these phenomena are largely due to properties of the tumours rather than of the host. The limitations of the technique to some cell lines and occasional primary tumours is obvious.

Animals↗
PubMed1983

Comparison between macroscopic and microscopic evaluation of tumour responsiveness using the subrenal capsule assay.

Using the subrenal capsule assay in normal mice, a histologic evaluation was made of 8 human primary ovarian tumours and 3 human colon, 2 lung and 5 ovarian carcinomas growing in serial passage in nude mice. The results of the evaluation indicated that there is a tumour- and drug-dependent correlation between the macroscopically and microscopically evaluated effects, with cyclophosphamide demonstrating excellent concordance but adriamycin and cisplatin both demonstrating consistently more tumour cell killing on histologic analysis than could be appreciated macroscopically. Leukocyte infiltration and fibrosis were greatly increased by the latter 2 drugs, leading to unrepresentative macroscopic measurements. Variable amounts of host cell infiltration can also be demonstrated in the untreated control when normal mice are used. The use of nude mice decreases the discrepancy between macroscopic and microscopic evaluation.

Animals↗
PubMed1978

Misonidazole with small dose fractions in an experimental osteosarcoma.

The mouse osteosarcoma C22LR was irradiated with a single X-ray dose of 1000 or 1500 rad (to prevent rapid growth) and then with fractionated doses of 300 or 600 rad each. Half the mice were given 0.8 mg/g of misonidazole 1 h before irradiation. Tumour growth delay was determined. The radiosensitizer did enhance the effect of small (300 rad) doses per fraction, as well as that of 600 rad doses.

Animals↗
PubMed1976

Studies on the enhancement by cyclophosphamide (NSC-26271) of artificial lung metastasis after labeled cell inoculation.

In a mouse model the retention of125I-5-iodo-2' -deoxyuridine-labeled tumor cells in the lung after iv injection was compared with the formation of tumor colonies in the lung 15 days after injection. The modification in lung retention after treatment with cyclophosphamide (CP), isophosphamide, Corynebacterium parvum, and heparin paralleled the changes in lung-colony numbers by these treatments. Since the modifications could be identified as early as 1 hour after iv administration of tumor cells, further evidence was obtained for the conclusion reached earlier that the modification of lung metastases by CP and Corynebacterium parvum is not due to immunologic mechanisms. Comparison with the lung retention of heat-killed tumor cells and living embryonic cells showed that CP induced an increased retention of all three cell types. In contrast, Corynebacterium parvum decreased the retention of living tumor cells, but failed to modify the retention of dead tumor cells, but did not affect the retention of living embryonic cells. Since no similar cell types were affected by the various treatments it seems likely that different mechanisms are involved. Apparently CP decreases the nonspecific resistance against the lodging and growth of any type of cell in the lung.

Animals↗
PubMed1975

Enhancement by drugs of metastatic lung nodule formation after intravenous tumour cell injection.

In studies on a model of induced pulmonary metastasis in mice a tumour host system was analysed which was not affected by immunogenicity of the tumour for the host; neither intensive immunosuppression nor immunization caused a significant change in the quantity of pulmonary metastatic nodules. In contrast the application of cytostatic drugs and of Corynebacterium parvum could modify the pulmonary resistance to the formation of tumour nodules by a factor greater than 100 in either direction. This finding confirms the observation of others that major modification of the resistance to metastatic tumour formation can occur independently of classical immunological mechanisms. Special attention is drawn to the fact that cyclophosphamide enhances the formation of metastatic nodules in this model by factors of 100 to more than 1,000 whereas other cytostatic drugs including the cyclophosphamide congeners iphosphamide and trophosphamide are active only factors between 2 and 12. The possible practical significance of these findings is discussed.

Alkylating Agents↗