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At least 19 recordsLinked to original sources
PubMed1989

Growth of human colorectal carcinoma implants in the mouse subrenal capsule assay.

The subrenal capsule assay (SRCA) in normal immunocompetent mice was performed from 1331 implants of 43 human colorectal carcinomas to evaluate the possible applications for clinical chemosensitivity testing. Also the effect of an immunosuppressive agent, cyclosporine, was tested on the growth of tumours. Histologically in all except one of 23 saline-treated tumours the original tumour tissue was replaced by granulation tissue and inflammatory cells. This was also true in cyclosporine-treated mice since in only one of the nine tests tumour cells were observed. The macroscopic growth of the implants in the cyclosporine-treated mice was significantly less than in the saline-treated mice. Flow cytometric DNA-analysis revealed that the difference between macroscopic growth of saline and cyclosporine-treated groups was observed only in DNA-diploid tumours. We conclude that new methods are required to preserve the viability of human colorectal carcinoma in the SRCA.

Animals↗
PubMed1987

[Analysis of the chemosensitivity test by human tumor clonogenic assay and subrenal capsule assay].

The antitumor activities of several chemotherapeutic agents were tested in the human tumor clonogenic assay (HTCA) and in subrenal capsule assay (SRCA). The results obtained in these two assays and clinical response were compared. 1. Colony growth was observed in 43 of 73 tumors (58.9%), and the adequate colony growth to evaluate the response of therapeutic groups was obtained in 21 tumors (28.8%). 2. Control growth adequate to meet evaluable assay criteria was obtained in 38 of 43 tumors (88.4%). 3. With activity criteria set at a decrease of greater than or equal to 50% in tumor colony-forming units for the HTCA and a change in tumor size less than or equal to -1.0 dmm for the SRCA, 24 of 98 drugs tested were active in HTCA (24.5%), and 50 of 160 drugs were active in SRCA (31.2%). 4. A total of 21 tumors was tested in both HTCA and SRCA and the tumor response was compared in 12 tumors treated with 39 drugs. Correlation of tumor responses between the two assays was 71.8%. 5. A total of 8 HTCA-clinical correlations and 5 SRCA-clinical correlations were possible. Overall predictive accuracy was 87.5% in the HTCA and 80.0% in the SRCA, respectively.

Antineoplastic Agents↗
PubMed1985

Clinical praxis and laboratory procedures in subrenal capsule assay (SRCA).

Subrenal capsule assay (SRCA) is a promising method in cancer research and in the selection of individual chemotherapy for cancer patients. The laboratory procedures of SRCA are as follows: on day zero 1 X 1 X 1 mm pieces of fresh human tumour are carefully prepared. The pieces are transferred by a trocar under the outer capsule of normal immunocompetent mice, one piece to each. The mice (about 30-40/test) are divided randomly into groups of at least five. The size of each piece (initial size) is measured in situ by a stereomicroscope fitted with an ocular micrometer. On days 1-5 cytostatics are administered to the animals. On day 6 the animals are killed and the final tumour size is measured. The difference between the final and initial tumour size describes the response of the tumour to the treatments. The critical point of the assay is the selection of the tumour fragment which has to be representative, as homogeneous as possible and contain living tumour cells. When the sample is in pieces of about 3 X 3 mm (4-5 tumour fragments are sufficient for the assay) in the culture medium, it may be stored in an ice bath or at room temperature for one day. During this time, though as rapidly as possible, the sample has to be delivered to a research laboratory where the SRCA is carried out.

Animals↗
PubMed1985

Response of ovarian cancer to combined cytotoxic agents in the subrenal capsule assay: Part I.

The subrenal capsule assay in normal immunocompetent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy. Of the assays, 42 were of untreated tumors and 19 of previously treated tumors. Fifty-nine (97%) of the assays were evaluable. The previously treated tumors were less sensitive than the untreated ones. Of the treated tumors 44% were sensitive, 33% intermediately sensitive, and 22% resistant versus 56, 44, and 0%, respectively, of the untreated tumors (P less than .01). Repeat assays for the tumors of seven patients were performed successfully after five to eight courses of therapy with the combination of doxorubicin, cyclophosphamide, and cisplatin. The responsiveness to this combination had weakened significantly (P less than .01); the response of only one tumor remained unchanged. The rates of resistance to the drug combinations doxorubicin-cyclophosphamide-cisplatin, doxorubicin-cyclophosphamide-tegafur, and cyclophosphamide-vincristine were 11, 10, and 21%, respectively; there was, however, considerable interindividual variation in tumor responses to these combinations. Of other combinations, hexamethylmelamine combined with 4-epidoxorubicin, aclarubicin, or chlorambucil and cisplatin had effect, whereas the combinations of cisplatin and etoposide and of tegafur and methotrexate or mitomycin were quite ineffective, as measured by the assay. The reliability of the subrenal capsule assay in normal immunocompetent mice is discussed, and it is concluded that the assay can be used to assess the response of ovarian cancer to chemotherapy, including multidrug therapy, without routine histologic control.

Aclarubicin↗
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↗
PubMed1983

Single agent chemotherapy for head and neck cancers. The murine subrenal capsule assay.

The murine subrenal capsule assay was used to determine chemotherapeutic sensitivities of metastatic, primary, or recurrent head and neck cancers. Tumor fragments (1 cu mm) were implanted under the renal capsule of 2- to 4-month-old normal female C57 BL/6 X DBA/2 F1 hybrid mice. Xenografts included 20 squamous cell carcinomas (SCCs), one mucoepidermoid carcinoma, one adenoid cystic carcinoma, and two melanomas. Groups of tumor-bearing mice were treated with chemotherapy daily for five days. Sensitivities of the tumor were assessed on day 6 by comparison of final implant size with initial implant size. Significant oncolytic activity was detected against 16 of 24 tumors (14 of 20 SCCs and both melanomas). Correlations between the in vivo assay and clinical studies are needed to determine its predictive value.

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↗
PubMed1990

[Chemotherapy responsiveness of brain tumors in subrenal capsule assay].

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.

Animals↗
PubMed1986

[Responsiveness of brain tumors to chemotherapeutic agents in the subrenal capsule assay].

The 6-day subrenal capsule assay was used to determine chemotherapeutic sensitivities of brain tumors. Twenty-nine brain tumors were obtained at the time of surgical resection. A minced tumor fragment (1-mm cube) was implanted under the renal capsule of 5- to 8- week-old normal female ddY mice. Each fragment was measured at two diameters using ocular micrometer unit (10 omu = 1.0 mm). The animals were randomized, usually 5 to 7 per group, and treated with anticancer drugs on day 1 through 5. On day 6, the mice were killed. The kidney was exteriorized and the tumor was again measured. The change in tumor size was obtained for each animal by ratio of the final tumor size/the initial tumor size. Sensitivities of tumors to anticancer agents were determined by comparing differences in mean values of the change in tumor size between control and treated group. Twenty-seven out of 29 specimens (93%) were submitted to evaluable assay. The response rate of 11 malignant gliomas (grade 3 and 4) was 44% and that to anticancer drugs tested were as follow: 5-FU 78%, ACNU and CPA 50%, VCR 40%, CDDP 36%. The response rate of 3 medulloblastomas was 36%: MTX 67%, CPA 50%, ACNU and CDDP 33%. That of two low-grade gliomas (grade 2) was 29%, while that of 4 malignant brain tumors (2 metastasis, chordoma, malignant fibrous histiocytoma) was 60%. Four neurinomas and 3 meningiomas were not sensitive to Tamoxifen and none were determined for estrogen receptor. In histological analysis, the transplanted tumor retained similar characteristics to the original tumor in the cases of neurinomas, meningiomas and some gliomas. Lymphocytic infiltration was observed in many cases. In the cases of metastasis (adenocarcinomas), considerable mesenchymation and lymphocytic infiltration was observed, tumor cells were reduced in number with poor preservation. Clinical response in 9 cases treated with sensitive drugs were 1 complete response, 2 partial response, 5 stable and 1 progressive disease in CT examination. The subrenal capsule assay is therefore considered to be very useful for determining suitable chemotherapeutic agents for brain tumors.

Animals↗
PubMed1985

Predictive testing of vulvar and cervical cancers to chemotherapy by the subrenal capsule assay.

The 6-day subrenal capsule assay (SRCA) in normal immunocompetent mice was used to assess response of vulvar and cervical cancers to chemotherapy. Twenty-five out of 31 assays (81%) were evaluable. The previously treated tumors tended to be less sensitive than the untreated tumors (20 vs 33%). Three to five cytotoxic drugs or drug combinations were tested against each individual tumor. In the whole material the combination of cisplatin and etoposide (VP-16) was significantly more effective than bleomycin (P less than 0.01, chi 2 test). The combinations adriamycin + cyclophosphamide + cisplatin and cyclophosphamide + methotrexate were also rather effective. Preliminary clinical correlations were positive. The reliability of the SRCA was discussed, and it was concluded that the assay is a promising predictive method for individualizing chemotherapy.

Adult↗
PubMed1989

Human renal cell carcinoma in the six day subrenal capsule assay.

The applicability of the subrenal capsule assay (SRCA) as a method for chemosensitivity testing of human renal cell carcinoma (RCC) was assessed. Tissue fragments of about one mm3. in size, obtained from patients who had undergone nephrectomy because of renal cell carcinoma (RCC), were implanted in preirradiated mice. The change of the size of the implanted tissue as well as the histology of the tissue were determined six days later. Untreated control tumors were used to determine the evaluability of the individual assays using criteria based on 1) tumor growth (an increase in tumor size or a decrease not exceeding 0.05 mm.) and 2) tumor histology (presence of carcinoma cells in at least 70% of the tissues). The first criterion was fulfilled in 20/24 (83%) of the renal tumors; tumor histology was satisfactory in 9/24 (38%) of the tumors. Taken together, only 9/24 assays were considered to be evaluable. Discrepancies between measurement and histologic appearance were also found for individual tumors and for treated tumors. Due to the lack of correlation between measurement and histology change in tumor size therefore cannot be considered a reliable parameter for assessing viability or drug activity.

Animals↗
PubMed1987

Comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) sensitivity tests of anticancer agents.

A comparative study on nude mice isotope assay (NM-IA) and subrenal capsule assay (SRCA) was done to evaluate the usefulness of in vivo assays for predicting individual tumor sensitivity against anticancer agents. Sixty-one fresh tumor specimens collected at surgery, under sterile conditions, were examined. Mitomycin C (MMC), 5-fluorouracil (5-FU), cyclophosphamide (CPM), adriamycin (ADM) and cis-DDPlatinum (CDDP) were used in both assays. In NM-IA, the tumor sensitivity was determined by the amount of 3H-thymidine incorporated into the tumor which had been implanted into subcutaneous spaces of BALB/c nude mice. In the SRCA, the relative increase in weight of the tumor implanted into the subrenal capsular space of ddY mice was determined and measurements made to evaluate the chemosensitivity. Evaluability rates of the trials were 86.9 per cent with both assays and the response rates were 35.8 per cent in NM-IA and 34.0 per cent in SRCA, respectively. Against MMC, 5-FU, CPM, ADM and CDDP, overall consistency rates between the two assays were 77.8 per cent, 88.6 per cent, 72.7 per cent, 81.8 per cent and 68.2 per cent, respectively. In 8 of these 53 evaluated assays, correlations between the results of assays and clinical effects were examined and overall predictive accuracy rates were 87.5 per cent with both assays. Significant differences between these two in vivo chemosensitivity tests were not evident.

Animals↗
PubMed1991

[Therapeutic efficacy of fosfomycin and cisplatin alone or in combination on human urogenital cancer by subrenal capsule assay].

Experimental therapies of human urogenital cancer with fosfomycin and cisplatin were performed by subrenal capsule assay. The subrenal capsule assay was applied for 10 cell lines, consisted of 4 renal cell carcinomas, 2 renal pelvic carcinomas, 2 carcinomas of the urinary bladder, one prostatic carcinoma, and one testicular tumor. The efficacy of each drug was evaluated by measuring the tumor growth, and compared the mean tumor volume of treated with that of untreated groups. The growth inhibition rate in fosfomycin group was 60% and in cisplatin group was 80%, whereas that of the combination therapy of both fosfomycin and cisplatin was 50%. This indicates that the combination therapy reduced the antitumor effect. Further, the histological findings also showed a similar pattern in both kidney and tumor tissues between the treated and untreated groups.

Animals↗
PubMed1987

[Clinical application of the subrenal capsule assay (SRCA) and related problems].

Subrenal capsule assay was performed on 35 fresh cancer tissue samples (13 stomach, 7 colon, 8 breast and 7 others) against MMC, 5-FU, ADM, CPA, MTX and cDDP employing normal immunocompetent ddY mice following Bogden's original method. Evaluability was 86% (30/35). Sensitivity was between 32 and 46% for each of the drugs except cDDP. Some organ-specific variations were noted between gastro-colic cancers and breast cancers with regard to chemosensitivity spectrum and also individual cases of the same histological type did not show a uniform one. Gastric cancer had the highest activity. The assay/clinical correlations were evaluable in 10 cases where 6 cases on active agents achieved two PR, two NC and PD, while all 4 cases on non-active agents showed PD. Histological analysis of implants, however, disclosed the following inherent problems: First, there was heterogeneity in tissue fragments due to the variable amounts of stroma; Second, apparent host reactions were seen in the untreated groups on the 6th day, accompanying marked damage to cancer cells. In contrast, in drug-treated groups, host reactions in most of them were suppressed and cancer cells were seen frequently in considerable amounts. This fact implies the mechanism that SRCA is based on, in spite of the xenograft immune; Third, there was some discordance between the macroscopic and microscopic findings. SRCA is assumed to be appliable to individual clinical cases up to a certain level which should be determined by histological analysis as well as by accumulation of clinically correlated cases.

Animals↗
PubMed1987

[Experimental and clinical studies on subrenal capsule assay for predicting individual tumor chemosensitivity].

Subrenal capsule assay (SRC assay) was investigated to evaluate the usefulness as an in vivo chemosensitivity test of anticancer agents. The pathological study on the growth of the implanted tumor and host response indicated that the assay had to be done by four-day assay. The analysis of the isotope incorporation into the implanted tumor supported this results. As determination of tumor sensitivity by the microscopic measurement showed the large standard deviation, the DNA and protein content was determined for the evaluation of sensitivity by percent inhibition of the DNA/protein content (%DNA/protein). Ninety five fresh tumor specimens were examined and evaluated by relative variation of the calculated tumor weight (delta TW/TW0), while 64 specimens by %DNA/protein. The evaluability rates using delta TW/TW0 and %DNA/protein were 84.2% and 87.5%, respectively. All over predictive accuracy between the clinical responses and the results of the assay evaluated by delta TW/TW0 was 78.6%, while 81.8% was obtained by %DNA/protein. From these results, the potential utility of SRC assay examined on 4 day for determining chemosensitivity by %DNA/protein seems to be beneficial for clinical use.

Animals↗
PubMed1987

[Clinical trials of the subrenal capsule assay].

Clinical trials of 4-day subrenal capsule assay (SRC assay) were carried out. One hundred and forty-one cases were investigated in order to evaluate the clinical utility of the assay. A total evaluability rate of 81.0% and a response rate of 36.5% were obtained in the SRC assay. The overall predictive accuracy between the tumor sensitivity of the assay and the clinical response was 82.1%. The percentage inhibition of %DNA/protein content of the implanted tumor, as a new predictor of the tumor growth inhibition, also indicated a good prediction rate for the assay. Correlation between the sensitivity test and the end results after chemotherapy in cases of inoperable gastric cancer classified as stage IV was investigated, retrospectively. Comparison of the survival curves between the patients treated with sensitive agents and those with insensitive agents exhibited a significant advantage for the former (p less than 0.01). These results suggest the utility of the SRC assay for clinical use, but histological studies exhibited certain limitations of this assay due to the existence of early host rejection of the implanted tumor. The utility of the SRC assay should be finally evaluated using more histological assessments and clinical trials.

Animals↗
PubMed1985

A histological assessment of the four-day subrenal capsule assay (SRCA).

A four-day subrenal capsule assay (SRCA) was developed, since fragments of human tumours implanted under the renal capsule of immunocompetent mice became rejected by the host within six days. The assay requires a histological assessment of both its exploitability and the extent of drug-induced anti-tumour lesions. 45 tumours from 43 patients with solid tumour were submitted to an SRCA in 1410 male B6D2F1 mice. After being biopsied each tumour was dissected by a pathologist, cut into 50 pieces (1.5 mm3), and one piece was implanted under the renal capsule of 35 mice; the mean tumour diameter was measured on day 0. The mice were randomized into groups of 6 to 10 animals each. On days 1, 2 and 3, the mice were treated with either placebo (control group) or with various anticancer agents. On day 4 the animals were sacrificed, the mean tumour diameter measured, the tumour bearing kidney fixed in Bouin's picroformol solution and processed for histological analysis after staining with hematein. Fragments of fresh explants of human tumours retained their proliferative and metabolic capacity: mitoses were observed as well as keratinizing cells in epidermoid carcinomas and melanin-producing cells in melanomas. Proliferation of tumour cells was seen along the renal capsule suggesting their affinity for connective tissue. Capillaries filled with mouse erythrocytes were also seen. No or minimal lymphocytic infiltration was found. Drug oncolytic effects ranged from minor cellular degeneration to almost complete necrosis and were documented by the scoring of histologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗