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Results for “Subrenal Capsule Assay”

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PubMed1991

A sequential immunosuppressive treatment with mizoribin (Bredinin) plus cyclosporin A on the subrenal capsule assay.

To minimize immunological interferences on the subrenal capsule (SRC) assay, a new immunosuppressor, mizoribin (MZB: Bredinin) alone or combined with cyclosporin A (ScA) was evaluated by an experimental SRC assay system using a rat ovarian cancer tissue. Daily applications of MZB (200 mg/kg) for 7 days following the xenograft of cancer tissue were insufficient to suppress immunological reactions of the recipient mice, and all the grafted cancer tissues were rejected. Although CsA monotreatment (60 mg/kg of CsA given daily for 7 days) successfully suppressed the host immune reaction, enhanced toxicities of CsA in combination with anticancer agents caused high lethal rate of host mice during the experimental chemotherapy. Sequential use of CsA on day 0 to day 2 followed by MZB on day 3, 5 and 7 brought the most favorable results with minimal host reactions and toxicities. An anticancer screening test using the modified SRCA accurately reflected the results of experimental chemotherapy against the rat ovarian cancer. The immunosuppressive treatment which minimizes immunological interferences with SRC assay chemoscreening test.

Animals↗

PubMed1989

The histological assessment and evaluation of a 4 day subrenal capsule assay by the percentage inhibition of DNA/protein.

A four day subrenal capsule assay was investigated in order to determine its ability to clinically predict tumor chemosensitivity. To establish more objective and accurate evaluation criteria, a histological assessment and measurement of the DNA and protein content of excised tumor implants was conducted in ddY mice. The histological studies provided qualitative results concerning the percentage of cancer cells in the xenograft, the number of mitoses, the amount of necrosis, and the extent of lymphocytic infiltration. The DNA content was measured by a modified version of the Schmidt-Thannhauser-Schneider method and the protein content was estimated using the Bio-Rad protein assay. The percentage of cancer cells in the xenograft correlated poorly with the relative increase in tumor size, weight and the percentage inhibition of DNA/protein (per cent DNA/protein), however, the per cent DNA/protein correlated well with the clinical effects in 85.7 per cent of the tumors studied. Moreover, the histological assessment information was only consistent with those results obtained for per cent DNA/protein in the control group.

Animals↗

PubMed1989

[Evaluation of the subrenal capsule assay (SRCA) in breast cancer using immunocompetent (NIC) mice].

UNLABELLED: To assess the value of subrenal capsule assay (SRCA) for predictive chemo-sensitivity testing in breast cancer 24 primary tumours were examined in normal immunocompetent (NIC; AB- and B6D2-F1-) mice. In 6 cancers the effect of 0.25 mg Prednisolone mous X day (applicated with drinking water) was compared to the control group. Independent of the mice-species a significant increase of the grafts size occurred in 14 of 20 evaluable cancers (p less than 0.05). Histologically the increase of tumour size was caused by infiltrated host cells, only in 22 of 107 (20.6%) grafts vitale tumour cells were detectable. After immunosuppression the increase of the grafts size was significant lower, than in the no treated control group (p less than 0.05). In groups treated with Prednisolone only a thin inflammatory host cell infiltration was observed, but vital tumour cells were only seen in 3 of 29 (10.3%) grafts. CONCLUSION: Using normal immunocompetent mice subrenal capsule assay is not suited for predicting responsiveness of breast cancers to cytostatic drugs.

Animals↗

PubMed1997

Mitotic index in the subrenal capsule assay as an indicator of the chemosensitivity of ovarian cancer.

The subrenal capsule assay (SRCA) is used in clinical oncology to assess the sensitivity of individual malignant tumors to various anticancer agents and their combinations. Mitotic indices reflect cancer cell proliferation and have prognostic value in epithelial neoplasms, including ovarian carcinoma. We combined the two tests (SRCA, mitotic index) by evaluating the numbers of mitotic figures per square millimeter of neoplastic epithelium (M/V) in paraffin-embedded tumor samples after SRCA. The M/V index was compared with the tumor size measurement (dTS), which is used in conventional SRCA to predict the drug response. Histology examination showed insignificant changes in the size of tumor transplants due to host reaction but disclosed a number of potential errors in the use of dTS to evaluate transplant growth and drug effects. In our series of 62 patients with advanced ovarian carcinoma the M/V value was superior to the dTS in explaining the clinical response after 6 months as assessed at second-look laparotomy. Patients showing no response had significantly higher M/V values than did those displaying complete or partial responses (P < 0.033). The use of 6 mitotic figures/mm2 as a limit differentiating responders from nonresponders resulted in an overall predictive accuracy of 79% in the logistic regression analysis. In comparison to the FIGO stage, residual tumor size, and the dTS, the M/V value obtained for the cytostatic combination given to the patient was the single most significant factor predicting the 6-month clinical response. The results indicate that the combined use of the M/V index and SRCA is a promising new approach to prediction of the drug response in ovarian adenocarcinoma.

Adenocarcinoma↗

PubMed1985

[Analysis of chemosensitivity against a human breast cancer xenograft (MX-1) with the subrenal capsule assay in BDF1 mice].

The antitumor activity of 27 anticancer drugs against a human breast cancer tumor (MX-1) has been studied using the subrenal capsule assay developed by A.E. Bogden et al. in 1978. Without immunosuppression with cyclophosphamide, BDF1 mice transplanted with MX-1 were treated with various drugs. The antitumor activity was evaluated by the tumor growth inhibition rate on day 6 after treatment. Among the 27 anticancer drugs tested, 10 compounds (37%) which showed more than 75% tumor growth inhibition rate were considered to be active. On the other hand, 8 compounds out of 27 drugs (30%) which showed less than 50% tumor growth inhibition rate were considered to be inactive. When the antitumor activity between the subrenal capsule assay in BDF1 mice and the subcutaneous transplantation assay in nude mice were compared, both assays were well correlated (r = 0.787, p less than 0.001). These results suggest that the antitumor activity of drugs can be evaluated faster, cheaper and easier by the subrenal capsule assay compared with the subcutaneous transplantation assay in nude mice.

Animals↗

PubMed1985

[Subrenal capsule assay, a new sensitivity test for antitumor agents].

The subrenal capsule assay (SRCA) has been developed by Bogden. This simple method using fresh human tumor has much more approximation with clinical procedure than other sensitivity tests. Even from our as yet limited small experiences, its high evaluability and high specificity are promising. Problems inherent to the actual assay and its limitations were reviewed and discussed, including our trial with bone marrow puncture specimens of leukemia, our evaluation criteria and assay-clinical correlations. This method will be widely utilized in several fields of cancer treatment in the near future.

Animals↗

PubMed1983

Effects of alpha and gamma interferons and cytostatics on ovarian cancer in the subrenal capsule assay.

Ovarian cancers from seven patients were grown in the subrenal capsule assay for 6 days in normal mice and for 12 days in nude mice. Groups of 5 mice received the following daily treatments: 1) saline 2) 6 x 10(5)IU of human leukocyte interferon (IFN-alpha) 3) 3 x 10(3)U of human IFN-gamma 4) 6 x 10(5)IU of IFN-alpha and 3 x 10(3)U of IFN-gamma 5) cytostatic drug combination (doxorubicin, cyclophosphamide, cis-platinum). The cytostatic drug combination had stronger antitumor activity than the interferons. The combination of alpha and gamma interferons was more effective than either interferons alone. The same trend was seen both in normal and nude mice.

Aged↗

PubMed1987

The subrenal capsule assay and gynecological cancer: five years of experience.

From 1982 through 1986 the subrenal capsule assay (SRCA) was used to test the sensitivity of 304 gynecological malignant tumors to cytotoxic drug combinations. Most of the tumors were ovarian cancers. Ninety-five percent of the assays were evaluable. Histological and ultrastructural studies were performed on transplants derived from ovarian cancers. Besides cytotoxic drugs, the activity of interferons was also studied by SRCA. Clinical comparisons were available in 43 patients with advanced disease; the predictive accuracy rate of the assay was 77%. The histological, ultrastructural and clinical studies indicated that SRCA is a reliable predictive test, which aids in the selection of proper therapy for individual patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

[Applicability of the subrenal capsule assay (SRCA) in primary breast carcinoma].

We have examined the application of the subrenal capsule assay (SRCA) by use of normal immunocompetent (NIC) mice for chemosensitivity testing of primary breast cancers. In 18 out of 20 carcinomas an evaluation was possible. AB mice (10 breast cancers) and B6D2-F1 mice (10 breast cancers) were taken as recipients. Measurement of the size and the histological examination of all transplants were obligatory performed before and after finishing the assay on day 6. By use of AB mice as well as B6D2 mice in each group in 6 out of 9 evaluable cancers occurred a significant growth of the transplanted tissues after 6 days (p less than 0.05). It could be demonstrated by the histological examination that the enlargement was a consequence of the immunological reaction of the NIC mouse to the xenogeneic material. In most cases (76 of 97 used mice) the transplants consisted of inflammation cells only. Vital tumor cells were seen only in few cases (21 of 97 used mice). It is concluded, that the SRCA is not suitable for chemosensitivity testing of human breast cancer, if NIC mice as recipients are used.

Animals↗

PubMed1991

The usefulness of cyclophosphamide pretreatment for subrenal capsule assay against human esophageal cancer.

In order to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pretreatment were compared to those obtained after cyclosporine A (CSA) treatment. CPM and CSA suppressed the host reaction until day 6 and day 12, respectively, however, the histological evaluation of the tumors on day 6 revealed no differences between the two groups. The cytotoxicity of CPM in mouse serum against P388 cells was measured to evaluate the residual activity of CPM against the implanted tumor. No cytotoxicity was observed in the serum 36 hours after the CPM injection. In the histological analysis of clinical samples, inflammatory infiltration was observed in only 4 of 25 samples and tumor cell preservation recognized in 27 of 28 samples. A persistence of tumor cells was recognized in the samples rich in tumor cells. Adequate growth of the tumor in the control groups was obtained from 30 of 33 tumors (91 per cent), and the response rates of this assay were comparable to those of prior clinical experiences on each of these drugs. These results indicated the feasibility of SRCA with CPM pretreatment as a predictive test of chemotherapeutic agents for esophageal cancer.

Animals↗

PubMed1988

[Experimental study of the 6-day subrenal capsule assay by cyclophosphamide pretreatment].

For the purpose to suppress the host immune reaction in subrenal capsule assay (SRCA) using normal immunocompetent mice, the effects of cyclophosphamide (CPM) pre-treatment (CPM 180 mg/kg day-1 s.c.) were compared with cyclosporine A (CSA) treatment (CSA 60 mg/kg s.c. daily). CPM and CSA suppressed host reaction until day 6 and day 12, respectively. However, in the histological evaluation of day 6 tumor, there was no difference between two groups. Mouse serum levels of CPM were measured by a bioassay as indicated by the cytotoxicity against P388 cells, to evaluate its residual activity against implanted tumor. No cytotoxicity was observed in the serum of 36 hr. after CPM injection. The antitumor activities of several chemotherapeutic agents against serially transplanted human esophageal cancer xenograft (IMEs-1) in untreated control group and CPM pre-treated group of SRCA were compared with the subcutaneous transplantation assay in nude mice. In all agents, the drug activities in CPM pre-treated group were similar to that in nude mice assay system. The increase of toxicity in CPM pre-treated group was very light. The immunosuppressive activity of CPM were also tested in 14 clinical samples. CPM suppressed the host reaction satisfactorily in all samples. These results suggest the usefulness of CPM pretreatment for suppressing the host reaction in SRCA.

Animals↗

PubMed1987

[Fundamental evaluation of the subrenal capsule assay as an in vivo chemosensitivity test].

Histological analyses of the subrenal capsule assay (SRCA) carried out with modification of Bogden's original method revealed that the major portion of cancer tissue implanted were almost replaced by the host immune cells and reactive tissue by day 6. For the purpose to find a more improved condition, the following experiments were performed using human cancer lines xenografted in nude mice. No prominent differences in the host reaction to xenograft were found between 3 kinds of immunocompetent mice. Subrenal space of the athymic nude mice allowed cancer tissue to grow well until 15 days after inoculation, and then chemosensitivity test to judge the growth inhibition rates. The similar condition as in nude mice was achieved in CDF1 mice by daily injection of 60 mg/kg of cyclosporin A.

Animals↗

PubMed1985

Ultrastructural effects of alpha and gamma interferons and cytostatics on ovarian cancer cells in the subrenal capsule assay (SRCA).

Ovarian cancers from 9 patients were grown in the subrenal capsule assay for 6 days. Groups of five mice were treated with saline, alpha interferon, a combination of alpha and gamma interferons and 2 cytostatic drug combinations with and without alpha interferon. The histological evaluation suggested that the regression of drug-treated transplants measured with stereomicroscope can reliably be used as an indicator of drug effect. However, it is possible that in a few cases the control growth measured with preparation microscope is somewhat exaggerated due to inflammatory reactions induced by the grafts. At the ultrastructural level, the cell, nuclear and mitochondrial volumes were morphometrically evaluated. The cytostatic treatment caused marked degenerative changes with nuclear enlargement and cytoplasmic vacuolization of the tumour cells. Only small differences could be detected between the control groups and the interferon-treated groups. In these groups, the nuclear and cytoplasmic volumes were not significantly different, whereas the mitochondrial volume was larger in the interferon-treated cells.

Animals↗

PubMed1987

[Successful chemotherapy with adriamycin and methotrexate in a case of advanced transitional cell carcinoma of the ureter--a clinical application of subrenal capsule assay].

A case of advanced transitional cell carcinoma of the left ureter was treated with a combination of adriamycin and methotrexate. These drugs were selected using the subrenal capsule assay for which tumor tissues were obtained from a biopsy specimen of the left supraclavicular lymph node. Complete regression of left supraclavicular lymph node metastasis and 90% regression of para-aortic lymph node metastasis were obtained after four courses of the combination therapy. Subsequently, left total nephro-uretrectomy and retroperitoneal lymph node dissection were carried out. Pathological examination revealed the remains of tumor cells in the primary lesion and in the para-aortic lymph node. The tumor tissues obtained from the para-aortic lymph node were not susceptible to adriamycin and methotrexate. However, the tendency of the regression rates in the drug-treated groups was the same as that apparent before chemotherapy. Three courses of the same regimen as that given before surgery were then prescribed. The patient is currently alive with no evidence of disease. We therefore suggest the usefulness of the subrenal capsule assay for predictive chemosensitivity testing.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1986

[Sensitivity test of anticancer agents by subrenal capsule assay (SRC assay). II--Determination of tumor sensitivity by percentage inhibition of DNA protein].

Subrenal capsule assay(SRC assay) has been reported to be an effective and rapid method for predicting the tumor sensitivity of individual patients to anti-cancer agents. In order to establish a more objective method of determining sensitivity in SRC assay the DNA content was measured by the schmidt-Thannhauser-Schneider method and the protein content was estimated using Bio-Rad protein assay, after removal of a tumor implanted in the subrenal capsular space of ddY mice. Percentage inhibition of DNA/protein had a high correlation with that of relative increase of tumor weight, although three groups treated with mitomycin-C, 5-fluorouracil and cyclophosphamide indicated different values of tumor sensitivity. From these results, the percentage inhibition of DNA/protein seems to be more objective than microscopic measurement for predicting tumor sensitivity.

Animals↗

PubMed1992

[Fundamental study of subrenal capsule assay by measuring specific activity of succinate dehydrogenase].

It may not show accurate results if subrenal capsule assay (SRCA) is made only by measuring tumor size, because of infiltration of host inflammation cells resulted from host immune reaction. We developed a new method which make possible an accurate determination of chemosensitivity by measuring specific activity of succinate dehydrogenase (SD) of the tumor cells implanted in the subrenal capsular space. With reference to SDI test, the assay condition for measuring specific activity of SD was determined. A comparative study was carried out in which malignant tumors of the oral cavity serially transplanted in nude mice were tested with SRCA and subcutaneous transplantation assay in nude mice. Chemosensitivity to peplomycin (PEP), CDDP and 5-fluorouracil (5-FU) evaluated SSDI method and nude mouse assay showed a high correlation than those evaluated by TGIR method and nude mouse assay. The overall predictive accuracy compared with nude mouse assay was 72.2% by TGIR method and 88.9% by SSDI method. SSDI method seemed to be a useful method to evaluate the chemosensitivity in SRCA.

Animals↗

PubMed1988

[Preclinical evaluation of a new anthracycline derivative, SM-5887 by subrenal capsule assay].

SM-5887, a new totally synthetic anthracycline derivative was evaluated the antitumor activity by subrenal capsule assay (SRCA) and the activity was compared to that of doxorubicin. The method of SRCA was the same originally developed by Bogden et al and 200 mg/kg of bredinin was administered subcutaneously 3 times every 2 days in order to induce immunosuppression of mice. Mice were given a single intravenous dose of either 30 mg/kg of SM-5887 or 15 mg/kg of doxorubicin. Fourty-four cases out of 64 were evaluable in this assay. The mean tumor growth inhibition rate (TGIR) in either SM-5887 or doxorubicin group was similar and the TGIRs of these two groups correlated well (y = 10.4 + 0.67x, p less than 0.01). Using more than 50% decrease of TGIR to define "sensitive", the chemosensitivity rates of SM-5887 and doxorubicin were 23% (10/44) and 25% (11/44) respectively. SM-5887 was effective to sarcomas and ovarian cancer especially. These results suggest that SM-5887 might have a similar antitumor activity compared to doxorubicin in clinical use.

Anthracyclines↗

PubMed1991

Subrenal capsule assay as a chemosensitivity test for primary esophageal squamous cell carcinoma.

The efficiency of the subrenal capsule assay (SRCA) was studied with fresh tissue of esophageal squamous cell carcinoma. The day-to-day changes in 10 carcinoma cases were evaluated for 9 days. The cancer cells continued to proliferate from the 3rd to the 7th day after the implantation and then decreased. The host reaction was recognized histologically from the 3rd or 4th day to the 9th day. However, the immune reaction did not significantly influence the evaluation of SRCA until the 7th day. The immunohistochemical staining with anti-bromodeoxyuridine monoclonal antibody revealed the existence of cancer cells at the DNA synthesizing stage (S stage) in the graft until the 7th day. In chemosensitivity test by SRCA, 21 patients were studied, and all were evaluable. 5-FU administration produced a response in 8/21 cases (38.1%), VDS in 8/21 (38.1%), and CDDP in 3/21 (14.3%). Used in combination, CDDP + VDS was effective in 7/18 cases (38.9%) and CDDP + BLM in 6/18 cases (33.3%).

Aged↗