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Results for “Subrenal Capsule Assay”

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PubMed1985

Antitumour effect of interferons, cytostatic drugs and their combinations in subrenal capsule assay (SRCA).

Combinations of interferons (IFNs) and cytostatic drugs were studied in subrenal capsule assay (SRCA) using fresh human ovarian cancer samples. Slight tumour growth inhibition was observed with IFN-alpha and IFN-gamma. The effect was more pronounced if combination IFN-alpha + IFN-gamma was used. Cytostatic drug combination cyclophosphamide + cisplatin + doxorubicin (combination I) was more effective than interferons, and combination methotrexate + tegafur (combination II) was about equal to IFN-alpha. When IFN-alpha was given together with cytostatic drugs, the antitumour effect was diverse: both synergistic and antagonistic effects were found, as well as no evidence of interaction. IFNs did not increase the toxicity of cytostatic drugs. If there is a good correlation between SRCA and clinical results, the combination of IFNs and cytotoxic drugs should be used clinically in connection with a predictive test.

Adult↗

PubMed1987

[Evaluation of chemosensitivity in the 6-day subrenal capsule assay].

The antitumor activity of chemotherapeutic agents can be evaluable faster by subrenal capsule assay (SRCA), and the activity ratings between SRCA and subcutaneous transplantation assay in nude mice were correlated well. Thus, SRCA can be utilized as a disease-oriented screening in vivo instead of a human tumor-nude mice system in the future. The original SRCA method developed by A.E. Bogden is a chemosensitivity test which is carried out in easy procedure. But because of infiltration of host cells derived by a host immune reaction, the chemosensitivity results in SRCA may be modified and so further work must be attempted to get exact results of chemosensitivity and good clinical correlation. Although, SRCA has a high possibility of application on an individual basis for prediction of chemosensitivity and it was discussed in this paper.

Animals↗

PubMed1994

Mouse subrenal capsule assay chemosensitivity and DNA flow cytometry parameters of human melanoma metastases.

Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry. The most effective combination was dacarbazine, vincristine, and carmustine (DOB), followed by cisplatin plus etoposide (Plat-VP16). By the original criteria of the assay, 35% of tumors were sensitive to DOB treatment while 15% responded to Plat-VP16. Chemosensitivity of DNA diploid and aneuploid tumors showed no significant difference; 35% of the aneuploid tumors were sensitive to DOB and 19% to Plat-VP16, whereas 41% and 13% respectively of the diploid tumors were sensitive. An association between DNA index and chemosensitivity was observed. Growth of the implant was observed in 44% of tumors with a DNA index above 1.5 receiving DOB treatment, whereas only 12% of tumors with an aneuploid DNA index < or = 1.5 grew. No significant difference was observed in the SPF of chemotherapy sensitive and insensitive tumors, though a tendency to lower SPF was observed in sensitive tumors.

Adult↗

PubMed1990

Evaluation of mizoribine as an immunosuppressant in subrenal capsule assay using immunocompetent mice.

We studied the application of mizoribine (MZR) to normal immunocompetent mice in subrenal capsule assay (SRCA) by means of tumor growth curve determination, histological analysis and autoradiography. At 400 mg/kg, MZR prolonged the actual tumor growth and moderately reduced the host reaction. Doses below 200 mg/kg did not effectively suppress the host reaction. The maximal weight loss of mice in the 400 mg/kg group reached 29%, but did not exceed 10% within 8 days. Hence, we applied 400 mg/kg of MZR to SRCA for up to eight days for cancer chemotherapy testing. This dose of MZR did not affect the labeling index of tumor cells compared with the control.

Animals↗

PubMed1987

[Chemosensitivity testing for 5-FU and 5-FU derivatives using subrenal capsule assay].

An evaluation was made, using in vivo subrenal capsule (SRC) assay, of the chemosensitivity of 12 human neoplastic tissues including 7 gastric cancers, 2 colo-rectal cancers, 2 lung cancers and 1 breast cancer, exposed to 5-fluorouracil (5-FU) and the 5-FU derivatives: tegafur (FT), UFT and hexylcarbamoyl-5-FU (HCFU). The relative variation of tumor size (delta TS/TS0) was calculated as follows: delta TS/TS0 = (TS6-TS0)/TS0 X 100 (%), where TS6 was the tumor size on day 6 and TS0 that on day 0, and more than a 10% decrease of delta TS/TS0 in the treated group was considered as positive for chemosensitivity. Delta TS/TS0 was decreased to -10.9 +/- 11.3% (mean +/- standard deviation) for 5-FU, -13.0 +/- 16.4% for FT, -19.8 +/- 18.2% for UFT and -18.8 +/- 15.1% for HCFU, and the inhibition of tumor growth following exposure to 5-FU correlated well with that following exposure to 5-FU derivatives (5-FU vs. FT, r = 0.659; 5-FU vs. UFT, r = 0.864; 5-FU vs. HCFU, r = 0.729). However, the sensitivity of each tumor varied; for example, the chemosensitivity was positive for 5-FU derivatives, but negative for 5-FU, in some tissues. The SRC assay appears to be useful for selecting sensitive drugs from 5-FU and 5-FU derivatives for individual cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Murine subrenal capsule assay: prediction of chemoresponsiveness in head and neck cancer.

If chemotherapy is to be used with the greatest efficacy in head and neck cancer, a predictive test that will indicate tumor sensitivity or resistance in individual patients may be desirable. This report demonstrates that the in vivo murine subrenal capsule assay was an efficient, sensitive method for retrospectively predicting the clinical response of squamous cell carcinomas of the head and neck to chemotherapy. Twenty-five courses of chemotherapy in 22 patients were compared to responses in the in vivo assay. The assay correctly identified sensitivity to chemotherapy in 86% of clinically responding patients. The specificity of the assay was 78%. A 60% efficiency for predicting clinical response and a 93% efficiency for predicting clinical resistance were demonstrated. Eighty percent of the results were correctly classified. The murine subrenal capsule assay has potential in planning of chemotherapy for selected patients.

Adult↗

PubMed1989

[Subrenal capsule assay applied to prediction of tumor radiosensitivity].

The radiation responses of murine fibrosarcomas with different radiosensitivities (MCA-induced fibrosarcoma and NFSa), human tumors transplanted into athymic nude mice (HeLa, HMV-I and SNG-II) and fresh surgical sample of human tumor (seminoma) were investigated using the subrenal capsule assay with immuno-competent C3H/He, C57BL and ICR mice as host. Mice were immuno-suppressed by the combination of cyclophosphamide and cyclosporin A. Tumor growth-speed of each transplant under the renal capsule of mice was much greater than that of the subcutaneous counterparts. Tumor responses under the renal capsule to radiation were well correlated with the known radiosensitivities of the tumors. Above findings indicate that the subrenal capsule assay is a feasible method to predict the radiation response of a tumor.

Animals↗

PubMed1987

[Analysis of clinical responses in comparison with the results of the chemosensitivity test by subrenal capsule assay].

We attempted to examine the practicality and the usefulness of 6-day subrenal capsule assay (SRCA) as a predictive chemosensitivity test. The success rate of this assay was 81% in 150 cases of various cancers. The drug sensitivity was evaluated by the inhibition rate of tumor growth (TGIR) on day 6 after drug treatment without immunosuppression of mice. We analyzed the clinical response in comparison with the results of SRCA in 38 cases in which transplanted tumor showed over 1.0 tumor growth rate (TGR). The average TGIR in these cases attained CR, PR, MR, NC and PD clinically were 60, 60, 49, 53 and 40%, respectively. The TGIR of CR and PR cases were significantly greater than that of PD cases (p less than 0.05). These results in SRCA correspond to clinically observed responses, using a greater than or equal to 45% inhibition in TGIR to define 'sensitivity'. Of 26 patients sensitive in SRCA, 18 patients (69%) showed true positive and 75% of patients (12 cases) resistant in the assay also failed to respond clinically (true negative). In the cases with less than 1.0 in TGR, a correlation between clinical responses and TGIR was not found. Based on these results, 6-day SRCA without immunosuppresive procedures can be utilized as a predictive chemosensitivity test for cancers which can grow over 1.0 in TGR in this assay system.

Animals↗

PubMed1987

[The subrenal capsule assay modified with three-dimensional measurement (volume method) and its higher predictivity].

Subrenal Capsule Assay (SRCA) developed by Bogden et al. is a new in vivo sensitivity test for anticancer agents. However, the presence of host reaction on about day 6 is largest problem for this method, and now many researchers are scrutinizing or introducing several modifications for this assay chiefly by immunosuppressing procedures. As one of the means to measure the actual change of the tumor volume and minimize the misreading of host reactions, we introduced three dimensional measurements of the grafts (volume method) instead of original mean diameter measurement. Using this method, prospective quantitative study was made. The results of 16 assays with 15 cases of miscellaneous malignancies showed 94% evaluability and in 22 treatments predictive accuracy was 77%. Assay/clinical correlation coefficient was 0.38 and coincidence of ranking order of the effectiveness was 6/6, with good contrast to those of 78%, 56%, 0.00 and 1/3, by original method respectively. Clinical responses more than PR were obtained in 9 of 15 cases. Two cases are still in CR for two years by assay directed single agent treatments. Many other minor modifications were also adopted and evaluated by quantitative observation of assay/clinical correlations. SRCA with our modifications seemed to have utilities than original.

Animals↗

PubMed1988

[A study of 6-day subrenal capsule assay with cyclophosphamide pretreatment--histological evaluation of clinical samples].

In order to suppress the host immune reaction in subrenal capsule assay (SRCA), effect of cyclophosphamide (CPM) was evaluated histologically in 25 fresh clinical samples. In 21 out of 25 clinical samples, the extent of lymphocyte infiltration was minimal, and in all samples the host reaction was suppressed significantly by CPM pretreatment. However, tumor cells were well preserved in only 10 out of 20 samples obtained from esophageal cancer patients. With the samples obtained from gastric and colorectal cancer patients, there were no tumor cells in the subrenal space on day 6. Persistence of tumor cells was well recognized in the samples having rich tumor and less stromal cells. The xenografts with moderately to well-preserved cancer cells showed an increase of the tumor size as expressed by delta TS. Though many xenografts showed a positive delta TS, preservation of tumor cells was poor. In each of the drug treated groups, a decrease of the tumor size and the histological effects were well correlated. It is suggested that 6-day SRCA with CPM pretreatment is useful as a chemosensitivity test, especially for the esophageal cancer whose tumor cells were well preserved.

Colonic Neoplasms↗

PubMed1990

[Preclinical evaluation of several cisplatinum analogs against human esophageal carcinoma by subrenal capsule assay].

The antitumor activities of CDDP analogs (CBD-CA, NK-121, 254-S) were evaluated preclinically by subrenal capsule assay (SRCA) with cyclophosphamide pretreatment. In the fundamental study, the antitumor activities against serially transplanted human esophageal cancer xenograft (IMEs-1) were compared with subcutaneous transplantation assay in nude mice and SRCA. The antitumor activities in SRCA were similar to those of in nude mice assay system (CBDCA greater than CDDP greater than 254-S greater than NK-121). Thus SRCA was considered to be useful for the evaluation of the activities of these agents. The activities were also tested against 10 human esophageal tumors obtained clinically. The sensitivity rate of these agents were 50% in CDDP, 30% in CBDCA, 30% in NK-121, and 30% in 254-S, respectively. These analogs seemed to be less effective than CDDP. However, in two cases, analogs were active though CDDP were inactive. The results suggest that these analogs are useful for the cases in which CDDP can not be given due to the toxicities and also for outpatient use.

Animals↗

PubMed1990

Subrenal capsule assay as a test to predict the effectiveness of chemotherapy in choriocarcinoma.

The value of the 6-day subrenal capsule assay (SRCA) in predicting the effectiveness of chemotherapy was tested using three human choriocarcinomas. The SRCA method proved to be a valuable chemopredictive test for choriocarcinoma. The results of experimental chemotherapy in nude mice and the results of the SRCA in two types of choriocarcinoma correlated well. Two of three choriocarcinomas showed sensitivity to MAC combination chemotherapy [methotrexate, actinomycin D, cyclophosphamide), and all three showed greater sensitivity to VP-16. The administration of VP-16 for treatment of all three types of choriocarcinoma significantly reduced tumor size in a dose-dependent fashion. From these observations, we speculate that the SRCA may be applied to assess the effectiveness of chemotherapy against human choriocarcinoma.

Animals↗

PubMed1987

Subrenal capsule assay for fresh human tumors in immunocompetent mice; an inappropriate technique for non-small cell lung cancer.

The subrenal capsule assay (SRA) seems to present some difficulties for the evaluation of the chemosensitivity of antineoplastic agents against fresh tumor xenografts. A study was therefore carried out to verify whether two different xenografts would behave in a similar way. Tumors such as melanoma provided adequate homogeneous material for this technique, while non-small cell lung carcinoma (NSCLC) were heterogeneous since the 1 mm3 specimen grafted under the renal capsule usually contained diffuse areas of necrosis and of infection. Furthermore, a large proportion of the grafted specimens, 257 out of 298, did not contain any tumor at all on microscopic examination even when they showed macroscopic growth. Added to these discrepancies, a random microscopic analysis of 180 adjacent fragments of NSCLC and melanomas demonstrated that the variability of heterogeneous tumors precludes any meaningful comparison between homologous tumor tissues designed to be grafted on treated and on control mice. The anti-inflammatory effect of chemotherapeutic drugs on the host's reaction to the graft is probably responsible for the differences between the macroscopic growth results observed in pieces grafted to both treated and control mice: however, it could not be simulated by hydrocortisone (HC) under our experimental conditions. This allows us to conclude that fresh tumors from NSCLC cannot be used in SRA.

Animals↗

PubMed1988

[Subrenal capsule assay as a chemosensitivity test (V)--Experimental chemotherapy of cyclosporin A-treated mice and nude mice].

We studied fundamentally subrenal capsule assay, using human tumor specimens (breast, gastric and colon cancers) serially transplanted in nude mice. Mitomycin C, 5-fluorouracil, adriamycin, cisplatinum or cyclophosphamide was injected into immunocompetent CDF1 mice treated with cyclosporin A (CsA) after tumor implantation. On day 6 and day 9 after inoculation, the chemosensitivity profiles of tumor xenografts were similar in CsA-treated mice and nude mice, macroscopically and microscopically. It is suggested that CsA-treated mice were an appropriate model as hosts for chemosensitivity testing. When we examine chemosensitivity effect macroscopically, a method of comparing chemotherapy groups with control groups; i.e. inhibition rate by measurement of tumor volume, was induced, in addition to the tumor size measurement. High toxicity due to cancer chemotherapeutic agents was found in CsA-treated mice, so that careful examination on treatment schedules with CsA and chemotherapeutic agents will be required.

Animals↗

PubMed1983

Chemotherapy responsiveness of human breast tumors in the 6-day subrenal capsule assay: an update.

Feasibility of utilizing the 6-day subrenal capsule (SRC) assay to screen drugs against fresh surgical explants of human tumors was confirmed by testing six clinically active chemotherapeutic agents against 141 human breast cancers. Response rates of the six drugs obtained in the assay compared favorably with clinical response rates for the same drugs as reported by Carter (5). The evaluable assay rate for breast tumors was 92% as compared to 89% for gynecologic tumors. Innate drug resistance was indicated with 16 of 57 tumors (28%) which did not respond to any of the six agents tested. Differences in responsiveness of tumors to each agent in a potential three-drug combination of either CMF or CAF suggest that the effectiveness of multiagent therapy might be enhanced if the individual agents of a potential drug combination were selected on the basis of tumor sensitivity to each of the agents in a predictive assay. Although cross-resistance between L-PAM and cytoxan was demonstrated and was statistically significant, 31% of these tumors responded individually to either one or the other agent, suggesting caution in extrapolating concomitance in activity between these two alkylators.

Animals↗

PubMed1996

[Evaluation of subrenal capsule assay (SRC) for clinical cancers].

For clinical cancers of esophagus (10 cases), stomach (7), colon and rectum (11) and breast (5), subrenal capsule assays (SRC) were performed using normal or AF nude mice. The sensitivity of anticancer drugs (UFT, CDDP) was evaluated by both the change in graft size under the renal capsule and the histological findings of these grafts. SRC was found to be a very reliable testing method for cancer of esophagus, colon and rectum because these grafts possessed remarkable viability. Evaluability of these two cancers was very high (approximately 80%). Sensitivity of UFT was 29% (2/7) for esophageal cancer, 50% (5/10) against colon and rectal cancer, and that of CDDP was 40% (2/5) and 17% (1/6), respectively. Evaluability of gastric and breast cancers was very low because of the poor growth of the grafts irrespective of the immunity of host animals. It was discussed why the evaluation rate depended on the type of cancer. These results suggest that indications for SRC are restricted, but that for colon and rectal or esophageal cancer SRC is a reliable testing method for anticancer drugs in clinical use.

Adult↗

PubMed1987

[In vivo chemosensitivity test for UFT and FT-207. I--Subrenal capsule assay].

A chemosensitivity test for UFT and FT-207, which are used in long-term administration clinically, was investigated for prediction of clinical response. Five transplantation-established human tumor xenograft systems were examined using subrenal capsule assay. Both anticancer agents showed antiproliferative effects according to the total administered dose. Two of 5 tumors were determined to be sensitive to UFT using microscopic measurements following intragastric administration of 1/2 of the LD50 value, while they were shown to be resistant to 5-FU. In these two cases, prolongation of life span by long-term administration of UFT was shown clinically. All these experiments could be performed on condition that the loss of body weight in mice was less than 20%. These results suggest that in the 4-day subrenal capsule assay, clinical responses to long-term administration of UFT or FT-207 are predictable using intragastric high-dose administration which does not induce more than 20% body weight loss in experimental mice.

Adenocarcinoma↗

PubMed1989

[An experimental study on subrenal capsule assay (SRCA)--problems for the use of immunosuppressive agents].

We studied whether or not cyclosporin A (CSA) has a usefulness in subrenal capsule assay (SRCA) with normal immunocompetent mice. Sixty mg/kg of CSA was given to BDF1 mice daily subcutaneously, and various dosages of adriamycin (ADR) was given intravenously on day 2. The body weight of BDF1 mice decreased over 20% within ten days when ADR was given at more than 5 mg/kg. MX-1, a human breast carcinoma line is known to be sensitive to ADR. This tumor was implanted subcutaneously in the back of BALB/c nu/nu mice and chemosensitivity was tested against ADR. ADR resulted to be positive at the dose of 8 mg/kg. On the contrary, the dose of 5 mg/kg proved to be negative, and hence the result of SRCA would be false negative, if the dose of ADR is reduced to avoid the toxicity of CSA. The tumor grew slowly when only 60 mg/kg of CSA was given daily for three weeks, and the inhibition rate was 56.2%. The toxicity of CSA was neglected because of the body weight loss was approximately 13%. CSA may have the antitumor effect by itself, and we therefore suggest that the CSA is not useful for SRCA.

Adenocarcinoma↗