Experimental mice for the development of an orthotopic model of bone malignancies.
Britta VormoorHenrike K. KniziaMichael A. BateyGilberto S. AlmeidaIan WilsonPetra DildeyAbhishek SharmaHelen BlairI. Geoff HideOlaf HeidenreichJosef VormoorRoss J. MaxwellChris M. Bacon
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Abstract Objective Orthotopic models are important in cancer research. Here we developed orthotopic xenograft mouse model of metastatic lung cancer and glioblastoma with a specially designed system. Methods Tiny fragments of surgical tumors were implanted into the mice brain with a trocar system. Immunohistochemistry was performed to detect brain tumor stem cells among glioblastoma tissues, including both the original and resulting ones with monoclonal antibody against CD133. Results Besides the constant high take rates in both models; brain transplants perfectly resembled their original tumors in biological behaviors. The brain tumor stem cells, positively stained with CD133 were found, though not frequently, in both original and resulting glioblastoma tissues. Conclusions Orthotopic model established with a trocar system is effective and injection of tumor tissues containing stem cells promise the forming of new tumor mass when grafted.
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Ovarian cancers are the leading cause of death among gynecologic tumors.Animal models are necessary for experimental cancer research and play an important role in the development of diagnostic and therapeutic modalities.The improvement of animal models to better simulate the conditions in patients is important for its role in the treatment for ovarian cancers.Orthotopic implantation is an attractive technique.Unlike heterotopic implantation,it allows a more accurate expression of the biologic nature of a human tumor,including growth,morphology and metastasis.The aim of the present study was to establish an orthotopic ovarian cancer model with high metastasis in nude mice.Human ovarian carcinoma cells HO-8910PM,a subline with highly metastatic potential,were inoculated subcutaneously in female nude mice to form solid tumors.The exuberantly growing tumor were removed,sliced and introduced into ovaries of other nude mice by microsurgical techniques.The growth and metastasis of the orthotopic lesion were followed,and pathological examinations were performed.Ovarian cancers formed in animals with an incidence of 57.14%.Metastatic lesions were detected in the lung,diaphragm,liver,stomach,intestine,pancreas,peritoneum,contralateral ovary and lymph nodes located in the iliac fossa,with an occurrence rate of 83.33% in animals.Transplanting tissues into the ovary of a nude mouse can form an orthotopic cancer model,and the manner how cancer spreads was similar to that of human lesions,which offers a remarkable model to explore ovarian cancers.
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Abstract Metastatic model of human tumor xenografts have been developed using orthotopic transplantation of histologically intact tissue (onplantation) of lung, stomach, colon, pancreatic, prostate and bladder carcinomas. These models represent the entire process of the metastasis, consisting of local tumor growth, vascular and lymphatic invasion at the local site, flow in the vessels and lymphatic, extravasation at the metastatic organs, and seeding and growth at relevant metastatic sites. Orthotopically transplanted human small‐cell lung carcinoma displayed a different chemosensitivity pattern compared with the subcutaneous transplanted model, suggesting different pharmacodynamics between the orthotopic lung and the ectopic subcutaneous sites. The intact‐tissue orthotopic‐onplantation model seems to be useful to study the mechanism of metastasis for discovery of antimetastatic agents and for the patient tumors and for this treatment design.
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Studies over the past decade have clearly shown that s.c. implant of primary and cultured tumor cells rarely leads to the occurrence of metastatic disease. Orthotopic transplantation of cell suspensions, surgical orthotopic implantation (SOI) of cancer tissue fragments resulted in metastases in many cancer types reaching 100% successful rate. We compared two metastatic models - heterotopic model of Lewis lung cancer and orthotopic B16 mouse melanoma. Both models were syngeneic with high metastatic ratio in C57BL/6 mice after transplantation of cancer cells, by injection into subcutaneous region of mice tail and without surgical intervention. The conclusion is that the localisation of cancer cell injection is a crucial condition for metastatic potential. The site with 100% haematogenous and lymph metastasis rate, after simple injection of cancer cells only, has been defined in mice, without dependence on the genetically predisposition and tumor cell line.
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Abstract Gastric carcinoma (GC) remains a leading cause of cancer related deaths worldwide with the 5‐year survival rate in the U.S. at ∼5% to 15% with existing therapies. This tumor is aggressive and has often metastasized to distant sites (liver, lung, and adjacent intestine) by the time of diagnosis. Treatment options (surgery, radiation, and chemotherapy) are limited and the disease carries a grave prognosis for most patients (50% 5‐year survival for distal GC; 10% 5‐year survival for proximal GC). An orthotopic model of human GC in nude mice provides an excellent way to evaluate the pathogenesis of tumor growth and metastasis in order to develop effective therapies, as well as to better understand the underlying biology of gastric tumor growth and metastasis. The protocol described in this unit details the development and characterization of an orthotopic model of human GC in athymic nude mice with diffuse lymphatic and hepatic metastatic spread. This model closely mimics the course of the human disease.
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