subrenal capsule assay


Summary: In vivo method of screening investigative anticancer drugs and biologic response modifiers for individual cancer patients. Fresh tumor tissue is implanted under the kidney capsule of immunocompetent mice or rats; gross and histological assessments follow several days after tumor treatment in situ.

Top Publications

  1. Migliavacca B, Nano R, Antonioli B, Marzorati S, Davalli A, Di Carlo V, et al. Identification of in vitro parameters predictive of graft function: a study in an animal model of islet transplantation. Transplant Proc. 2004;36:612-3 pubmed
    ..75 with 2000 IE) correlated with transplant success. These data show that purity of islet preparations and their insulin content should be useful parameters for the selection of islet preparations for transplant purposes. ..
  2. Lee C, Xue H, Sutcliffe M, Gout P, Huntsman D, Miller D, et al. Establishment of subrenal capsule xenografts of primary human ovarian tumors in SCID mice: potential models. Gynecol Oncol. 2005;96:48-55 pubmed
  3. Goto K, Salm S, Coetzee S, Xiong X, Burger P, Shapiro E, et al. Proximal prostatic stem cells are programmed to regenerate a proximal-distal ductal axis. Stem Cells. 2006;24:1859-68 pubmed
    ..Together, these novel findings illustrate features of primitive prostate cells that may have implications for the development of therapies for treating proliferative prostatic diseases. ..
  4. Yoshida S, Kajimoto Y, Yasuda T, Watada H, Fujitani Y, Kosaka H, et al. PDX-1 induces differentiation of intestinal epithelioid IEC-6 into insulin-producing cells. Diabetes. 2002;51:2505-13 pubmed
  5. Flier S, Kulkarni R, Kahn C. Evidence for a circulating islet cell growth factor in insulin-resistant states. Proc Natl Acad Sci U S A. 2001;98:7475-80 pubmed
    ..These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity. ..
  6. Yonemoto M, Satoh T, Arakawa H, Suzuki Takahashi I, Monden Y, Kodera T, et al. J-104,871, a novel farnesyltransferase inhibitor, blocks Ras farnesylation in vivo in a farnesyl pyrophosphate-competitive manner. Mol Pharmacol. 1998;54:1-7 pubmed
    ..Furthermore, J-104,871 suppressed tumor growth in nude mice transplanted with activated H-ras-transformed NIH3T3 cells. ..
  7. Marek J, Bechynĕ M. The subrenal capsule assay in immunocompetent mice--the inevitable role of histopathology in assessment of this method as a tool determining tumor sensitivity to cytostatic drugs. Neoplasma. 1990;37:23-30 pubmed
    The subrenal capsule assay (SRC) in immunocompetent mice became one of commonly used approaches to evaluating the efficiency of cytostatic therapy...
  8. Sekiguchi I, Suzuki M, Aida I, Tamada T, Nishida M. [Responsiveness of gynecological malignancies to oral antitumor agents in subrenal capsule assay and individualization of oral adjuvant chemotherapy]. Nihon Sanka Fujinka Gakkai Zasshi. 1990;42:437-42 pubmed
    A subrenal capsule assay (SRCA) was performed to test the sensitivity of 45 gynecological malignancies, including 24 cervical and 15 ovarian carcinomas, to oral antitumor agents, UFT, cyclophosphamide (CPM) and carboquone (CQ)...
  9. Johansson U, Elgue G, Nilsson B, Korsgren O. Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation. Am J Transplant. 2005;5:2632-9 pubmed

More Information


  1. McLean A, D Amour K, Jones K, Krishnamoorthy M, Kulik M, Reynolds D, et al. Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells. 2007;25:29-38 pubmed
    ..These findings have important implications for our understanding of hESC self-renewal and early cell fate decisions. ..
  2. Kampf C, Lau T, Olsson R, Leung P, Carlsson P. Angiotensin II type 1 receptor inhibition markedly improves the blood perfusion, oxygen tension and first phase of glucose-stimulated insulin secretion in revascularised syngeneic mouse islet grafts. Diabetologia. 2005;48:1159-67 pubmed
    ..Such treatment should not be initiated, however, before the islet vascular system has been formed. ..
  3. Seminara P, Bogdanov G, Codacci Pisanelli G, Leonetti C, Konovalova N, Diatchkovskaya R, et al. Comparative in vitro and in vivo study of a nitroxyl derivative of 5-fluorouracil (magnizil) on human gastrointestinal tumors. Tumori. 1995;81:278-82 pubmed
    ..The activity of both the drugs against human tumors was also assessed in mice with the subrenal capsule assay. A similar cytotoxic activity was found for magnizil and 5-fluorouracil on the HT29 cell line...
  4. Fukushima H. Subrenal capsule assay using liver cancer specimens obtained by fine needle biopsy. Kurume Med J. 1991;38:181-6 pubmed
  5. Wennberg L, Sundberg B, Ekdahl Nilsson K, Korsgren O. C-Peptide determinations in islet xenotransplantation: A study in the pig-to-mouse model. Cell Transplant. 2001;10:165-73 pubmed
    ..Consequently, determinations of donor-specific C-peptide may not properly reflect islet xenograft function. In fact, islet xenograft function may be underestimated. ..
  6. Yoon I, Choi S, Kim Y, Yang S, Park J, Park C, et al. Pancreatic islets induce CD4(+) [corrected] CD25(-)Foxp3(+) [corrected] T-cell regulated tolerance to HY-mismatched skin grafts. Transplantation. 2008;86:1352-60 pubmed publisher
    ..Unmanipulated pancreatic islets can induce immunologic tolerance associated with peripherally induced CD4+Foxp3+ Tregs, a significant proportion of which notably are CD25-. ..
  7. Hara H, Ohdan H, Tokita D, Onoe T, Zhou W, Asahara T. Construction of ectopic xenogeneic bone marrow structure associated with persistent multi-lineage mixed chimerism by engraftment of rat bone marrow plugs into mouse kidney capsules. Xenotransplantation. 2003;10:259-66 pubmed
    ..Thus, engraftment of BM plugs into the kidney capsules results in the construction of a donor-derived BM microenvironment, facilitating multilineage mixed xenogeneic chimerism. ..
  8. Sawada T, Matsumoto I, Nakano M, Kirchhof N, Sutherland D, Hering B. Improved islet yield and function with ductal injection of University of Wisconsin solution before pancreas preservation. Transplantation. 2003;75:1965-9 pubmed
    ..05, group 2 vs. group 3 and group 4 vs. group 5). Ductal preservation improved islet yield and function after 6 and 24 hr of preservation. Well-preserved pancreatic ducts maintained good distribution of collagenase solution. ..
  9. Munakata H, Kawahara M, Kayada Y, Sakamoto T, Takada K. [Fundamental study of subrenal capsule assay by measuring specific activity of succinate dehydrogenase]. Gan To Kagaku Ryoho. 1992;19:217-22 pubmed
    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...
  10. Brewer L, LaRue R, Hering B, Brown C, Njenga M. Transplanting encephalomyocarditis virus-infected porcine islet cells reverses diabetes in recipient mice but also transmits the virus. Xenotransplantation. 2004;11:160-70 pubmed
    ..EMCV infection does not appear to affect insulin production by PICs, but infected xenografts can transmit the virus to recipient animals, resulting in severe disease. ..
  11. Bucher P, Mai G, Mathe Z, Bosco D, Pernin N, Berney T, et al. Retransplantation of discordant xenogeneic islets with costimulatory blockade. Transplant Proc. 2004;36:1201-2 pubmed
    ..MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies. ..
  12. Staudt M, Kanan Y, Jeong J, Papin J, Hines Boykin R, Dittmer D. The tumor microenvironment controls primary effusion lymphoma growth in vivo. Cancer Res. 2004;64:4790-9 pubmed
    ..These findings underscore the importance of the microenvironment for PEL tumorigenesis and simplify the preclinical evaluation of potential anticancer agents. ..
  13. Shatry A, Levy R. Engraftment of splenic tissue as a method to investigate repopulation by hematopoietic cells from host and donor marrow. Stem Cells Dev. 2004;13:390-9 pubmed
    ..In summary, this method should provide a useful model for the transfer of the splenic microenvironment to study the biology of the spleen in non-transplant and BMT settings. ..
  14. Muhonen T, Pyrhonen S, Laasonen A, Wasenius V, Asko Seljavaara S, Franssila K, et al. Mouse subrenal capsule assay chemosensitivity and DNA flow cytometry parameters of human melanoma metastases. Acta Oncol. 1994;33:431-7 pubmed
    Chemosensitivity was analyzed by mouse subrenal capsule assay (SRCA) in 103 human melanoma metastases 79 of which were also analyzed by DNA flow cytometry...
  15. Heisterkamp J, van Hillegersberg R, Ijzermans J. Critical temperature and heating time for coagulation damage: implications for interstitial laser coagulation (ILC) of tumors. Lasers Surg Med. 1999;25:257-62 pubmed
    ..These data can be used to achieve complete tumor destruction and minimal surrounding tissue damage during real-time MR-controlled ILC. ..
  16. Mathews C, Langley S, Leiter E. New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation. 2002;73:1333-6 pubmed
  17. Thomas M, Wang X, Hornsby P. Human adrenocortical cell xenotransplantation: model of cotransplantation of human adrenocortical cells and 3T3 cells in scid mice to form vascularized functional tissue and prevent adrenal insufficiency. Xenotransplantation. 2002;9:58-67 pubmed
    ..This demonstrates that transplanted human endocrine cells can functionally replace a surgically removed endocrine organ in a host animal. ..
  18. Joo S, Choi B, Kang M, Jung D, Park K, Park J, et al. Development of functional human immune system with the transplantations of human fetal liver/thymus tissues and expanded hematopoietic stem cells in RAG2-/-gamma(c)-/- MICE. Transplant Proc. 2009;41:1885-90 pubmed publisher
    ..The results of this study demonstrated a practical mouse model of expanded human immune cells especially T cells in Rag2(-/-)gamma(c)(-/-) mice. ..
  19. Cutz J, Guan J, Bayani J, Yoshimoto M, Xue H, Sutcliffe M, et al. Establishment in severe combined immunodeficiency mice of subrenal capsule xenografts and transplantable tumor lines from a variety of primary human lung cancers: potential models for studying tumor progression-related changes. Clin Cancer Res. 2006;12:4043-54 pubmed
    ..The transplantable tumor lines seem to provide good models for studying various aspects of tumor progression and a platform for developing novel therapeutic regimens, with the possibility of patient-tailored therapies. ..
  20. Master V, Wei G, Liu W, Baskin L. Urothlelium facilitates the recruitment and trans-differentiation of fibroblasts into smooth muscle in acellular matrix. J Urol. 2003;170:1628-32 pubmed
    ..Smooth muscle development during augmentation with acellular matrix is facilitated by the placement of epithelia onto the surface of the matrix. ..
  21. Kubo M, Sonoda Y, Muramatsu R, Usui M. Immunogenicity of human amniotic membrane in experimental xenotransplantation. Invest Ophthalmol Vis Sci. 2001;42:1539-46 pubmed
    ..The amniotic membrane may be useful to supplement corneal collagen, and it may be applied not only to the ocular surface but also intracorneally. ..
  22. Park M, Han C, Lee K, Hong S, Kim H, Lee Y, et al. Effects of activin A on pancreatic ductal cells in streptozotocin-induced diabetic rats. Transplantation. 2007;83:925-30 pubmed
    ..The pancreatic ductal cells could be efficiently differentiated into insulin secreting cells by activin A treatment in vitro and normalize hyperglycemia in vivo. ..
  23. Larsen R, Bruland O. Intratumour injection of immunoglobulins labelled with the alpha-particle emitter 211At: analyses of tumour retention, microdistribution and growth delay. Br J Cancer. 1998;77:1115-22 pubmed
    ..The heterogeneous tumour dose distribution observed is, however, a major impediment to the use of alpha-particle emitters against solid tumours. ..
  24. Kin T, Rajotte R, Dufour J, Korbutt G. Development of an immunoprivileged site to prolong islet allograft survival. Cell Transplant. 2002;11:547-52 pubmed
  25. Venesmaa P, Ylikorkala O. Subrenal capsule assay in selection of chemotherapy after operation for recurrent ovarian cancer. Br J Cancer. 1991;63:84-6 pubmed
    Forty-six patients with recurrent ovarian cancer were reoperated, and cancer samples for the subrenal capsule assay (SRCA) were collected from 23 of them, whereas this test was not done in the remaining 23 control patients...
  26. Waalkes M, Diwan B. Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. Carcinogenesis. 1999;20:65-70 pubmed
    ..These studies show cadmium can effectively reduce growth and progression of human lung carcinoma xenografts in a fashion that is probably independent of apoptosis. ..
  27. Barbarics E, Kronauge J, Davison A, Jones A. Uptake of cationic technetium complexes in cultured human carcinoma cells and human xenografts. Nucl Med Biol. 1998;25:667-73 pubmed
  28. Ko S, Kwon H, Suh S, Yang J, Kim S, Ahn Y, et al. Dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine neonatal pancreas cell clusters (NPCCs) into beta-cells in normal nude mice. Diabetes Res Clin Pract. 2004;66 Suppl 1:S97-S101 pubmed
    ..Our results suggest that dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine NPCCs into beta-cells in normal nude mice. ..
  29. Drage M, Zaccone P, Phillips J, Nicoletti F, Dawson J, Andrew Bradley J, et al. Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice. Transplantation. 2002;74:611-9 pubmed
    ..Insulin therapy improves graft survival in mice treated with YTS177. Preventing the action of IL-1 greatly improves graft survival induced with YTS177. ..
  30. Kayama M, Kurokawa M, Ueda Y, Ueno H, Kumagai Y, Chiba S, et al. Transfection with pax6 gene of mouse embryonic stem cells and subsequent cell cloning induced retinal neuron progenitors, including retinal ganglion cell-like cells, in vitro. Ophthalmic Res. 2010;43:79-91 pubmed publisher
    ..Cloned cell lines may be useful to analyze the requirements for retinal progenitor cell differentiation, and our study suggests the clinical application of this cell type. ..
  31. Sun B, Chen M, Hawks C, Hornsby P. Immortal ALT+ human cells do not require telomerase reverse transcriptase for malignant transformation. Cancer Res. 2005;65:6512-5 pubmed
    ..method is used as an assay for tumorigenicity, hTERT may be artifactually scored as an oncogene; the subrenal capsule assay shows that ALT, as a telomere maintenance mechanism, is equivalent to hTERT in neoplastic transformation ..
  32. Hara Y, Fujino M, Nakada K, Kimura K, Adachi K, Li X. Influence of the numbers of islets on the models of rat syngeneic-islet and allogeneic-islet transplantations. Transplant Proc. 2006;38:2726-8 pubmed
    ..In conclusion, higher frequencies of primary nonfunction occurred with less than 1500 islets transplanted. They were independent of the sites in the rat-islet transplantation model. ..
  33. Schirner M, Hoffmann J, Menrad A, Schneider M. Antiangiogenic chemotherapeutic agents: characterization in comparison to their tumor growth inhibition in human renal cell carcinoma models. Clin Cancer Res. 1998;4:1331-6 pubmed
    ..Further characterization of antiangiogenic compounds considered for clinical application should, however, have its focus on slow-growing tumors, which are not accessible for most therapeutic strategies. ..
  34. Stagner J, Mokshagundam S, Wyler K, Samols E, Rilo H, Stagner M, et al. Beta-cell sparing in transplanted islets by vascular endothelial growth factor. Transplant Proc. 2004;36:1178-80 pubmed
    ..The provision of exogenous VEGF may be a useful adjunct to islet transplantation. ..
  35. Wang Y, Hayward S, Donjacour A, Young P, Jacks T, Sage J, et al. Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res. 2000;60:6008-17 pubmed
  36. Medarova Z, VALLABHAJOSYULA P, Tena A, Evgenov N, Pantazopoulos P, Tchipashvili V, et al. In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation. 2009;87:1659-66 pubmed publisher
    ..This study establishes a method for the noninvasive, longitudinal detection of pancreatic islets transplanted into non-human primates using a low-field clinical MRI system. ..
  37. Crutchlow M, Yu M, Bae Y, Deng S, Stoffers D. Exendin-4 does not promote Beta-cell proliferation or survival during the early post-islet transplant period in mice. Transplant Proc. 2008;40:1650-7 pubmed publisher
  38. Furman W, Stewart C, Poquette C, Pratt C, Santana V, Zamboni W, et al. Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children. J Clin Oncol. 1999;17:1815-24 pubmed
    ..These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials. ..
  39. Butcher G, Couchman A, Van Pelt J, Fleck S, Sinden R. The SCID mouse as a laboratory model for development of the exoerythrocytic stages of human and rodent malaria. Exp Parasitol. 1993;77:257-60 pubmed
  40. Su C, Chen X, Zhang Z, Gu W, Zhang M, Zhou G, et al. [Protective effect of heme oxygenase-1 induction in vivo to pancreas islet xenograft]. Zhonghua Wai Ke Za Zhi. 2009;47:1249-52 pubmed
    ..The higher expression of HO-1 induced by CoPP in vivo would significantly prolong graft survival time and its mechanism could be related to immune modulation of IL-10. ..
  41. McNamara D, Cook P, Allen L, Kehoe M, Holland C, Teepe A. Synthesis, antitumor activity, and antiviral activity of 3-substituted 3-deazacytidines and 3-substituted 3-deazauridines. J Med Chem. 1990;33:2006-11 pubmed
    ..Compound 1 also displayed significant activity against rhinovirus type 34. ..
  42. Tung W, Wang Y, Gout P, Liu D, Gleave M, Wang Y. Use of irinotecan for treatment of small cell carcinoma of the prostate. Prostate. 2011;71:675-81 pubmed publisher
  43. Trencsenyi G, Kertai P, Bako F, Hunyadi J, Marian T, Hargitai Z, et al. Renal capsule-parathymic lymph node complex: a new in vivo metastatic model in rats. Anticancer Res. 2009;29:2121-6 pubmed
    ..The renal capsule-parathymic lymph node complex seems to be suitable for the isolated in vivo examination of metastatic development and for the detailed analysis of secondary tumors. ..
  44. Shimizu I, Fudaba Y, Shimizu A, Yang Y, Sykes M. Comparison of human T cell repertoire generated in xenogeneic porcine and human thymus grafts. Transplantation. 2008;86:601-10 pubmed publisher
    ..Human thymocytes in human thymus grafts are not tolerized by the presence of an additional porcine thymus, but tolerance might be achieved by postthymic encounter with porcine antigens. ..
  45. Wen Z, Zhang T, Rong T. [Clinical adjuvant chemotherapy base on chemosensitivity in nude mouse subrenal capsule assay for non-small cell lung cancer]. Ai Zheng. 2003;22:1355-8 pubmed
    ..the survival period by postoperative adjuvant chemotherapy base on chemosensitivity testing in nude mouse subrenal capsule assay. Fresh NSCLC specimens were transplanted into nude mouse subrenal capsule and 10 kinds of potential ..
  46. Okamoto N, Chihara R, Shimizu C, Nishimoto S, Watanabe T. Artificial lymph nodes induce potent secondary immune responses in naive and immunodeficient mice. J Clin Invest. 2007;117:997-1007 pubmed
    ..Our results indicate that aLNs support strong antigen-specific secondary antibody responses in immunodeficient mice and suggest the possibility of future clinical applications. ..
  47. Miao G, Ostrowski R, Mace J, Hough J, Hopper A, Peverini R, et al. Dynamic production of hypoxia-inducible factor-1alpha in early transplanted islets. Am J Transplant. 2006;6:2636-43 pubmed
  48. Masaki H, Appel M, Leahy L, Leif J, Paquin L, Shultz L, et al. Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice. Xenotransplantation. 2006;13:224-32 pubmed
    ..Chimerism permits prolonged xenograft survival, but chimerism generated in this way is unstable over time. Skin xenografts are eventually rejected, whereas most islet xenografts survive long term and perhaps permanently. ..
  49. Ohashi K, Kay M, Yokoyama T, Kuge H, Kanehiro H, Hisanaga M, et al. Stability and repeat regeneration potential of the engineered liver tissues under the kidney capsule in mice. Cell Transplant. 2005;14:621-7 pubmed
  50. Munakata H, Kayada Y, Kawahara M, Sakamoto T, Yoshiga K, Takada K. A biochemical evaluation of oral squamous cell carcinoma growth by measurement of specific activity of succinate dehydrogenase in the subrenal capsule assay. Int J Oral Maxillofac Surg. 1995;24:216-20 pubmed
    An auxiliary method for determination of chemosensitivity with the subrenal capsule assay (SRCA) was developed in which the specific activity of succinate dehydrogenase (SD) of tumor implanted beneath the renal capsule is measured...
  51. Sunagawa M, Suzuki T, Ito K, Endo M. Subrenal capsule assay as a chemosensitivity test for primary esophageal squamous cell carcinoma. J Surg Oncol. 1991;46:71-6 pubmed
    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...
  52. Muhonen T, Pyrhonen S, Laasonen A, Wasenius V, Asko Seljavaara S, Franssila K, et al. Tumour growth rate and DNA flow cytometry parameters as prognostic factors in metastatic melanoma. Br J Cancer. 1992;66:528-32 pubmed
    ..75 (P less than 0.0001). This score was the most significant (P less than 0.0001) prognostic factor in the Cox model when TNM stage, age, ploidy, SPF, and tumour growth rate were analysed as covariates. ..
  53. Suarez Pinzon W, Rabinovitch A. Combination therapy with epidermal growth factor and gastrin delays autoimmune diabetes recurrence in nonobese diabetic mice transplanted with syngeneic islets. Transplant Proc. 2008;40:529-32 pubmed publisher
    ..We concluded that the EGF plus gastrin combination therapy inhibited the recurrent autoimmune response and delayed rejection of syngeneic islet grafts, suggesting a therapeutic role for these peptides in islet transplantation. ..