Orthotopic tumors

After tumor removal, the skin is closed with sterile, stainless steel wound clips. In most cases, primary orthotopic tumors have not invaded into the abdominal wall and so this remains intact. 

Dil CIS-labeled liposomes were administered via tail vein of orthotopic tumor model mice (7) on the day 3, 9 and 18 after tumor implantation. Two hours after injection of liposomes, mice were sacrificed and the tumor was dissected. Then, these sections were fiuorescently observed by using a microscopic LSM system (Carl Zeiss, Co., Ltd.) (Fig. 2). 

Epperly MW, Defilippi S, Sikora C et al. (2000a) Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthotopic tumors from irradiation. Gene Ther 7 1011-1018... 

Brigger I, Morizet J, Laudani L, Aubert G, Appel M, Velasco V, Terrier-Lacombe MJ, Desmaele D, d Angelo J, Couvreur P, Vassal G (2004) Negative preclinical results with stealth) (R)) nano-spheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model. Journal of Controlled Release 100 29 10. 

Inhibition of IGF-IR autophosphorylation by NVP-ADW742 results in a plethora of pro-apoptotic molecular events that may account for its effectiveness as a single agent and in enhancing the antitumor activity of a broad spectrum of chemotherapeutic and anticancer targeted agents. Initial in vivo proof-of-concept of the potential therapeutic benefit of blocking IGF-IR kinase activity in tumor cells was obtained in an orthotopic multiple myeloma (MM) model of bone and bone marrow disease. In this mice model, MM... 

Peliosis hepatis has been described in association with contraceptive-induced hepatic tumors and has sometimes developed in isolation, perhaps as a herald of more serious changes to follow, for example cirrhosis and portal hypertension one such case ultimately required an orthotopic liver transplant (219). 

Key words Metastasis, autochthonous tumors, genetically engineered tumor models, orthotopic... 

Alternatively, models of spontaneous metastasis from a primary tumor at either a subcutaneous site or better an orthotopic site may be used. Because of rapid primary tumor growth it is often resected to allow time for metastases to grow. Therefore, multiple metrics, including number of metastases, metastatic sites, relapse rate, time to recurrence, tumor growth rate, survival and... 

Clinical observations have suggested that the organ environment can influence the response of tumors to therapy. For example, in women with breast cancer, lymph node and skin metastases are more sensitive to chemotherapeutic intervention than metastases in either the lung or the bone (34). Similarly, orthotopic implantation of human tumor cells from surgical specimens into nude mice has shown that colon carcinomas injected into the wall of the colon, results in more clinically relevant outcomes then subcutaneously injected colon carcinomas. Orthotopic implanta-... 

One of the obvious advantages of orthotopic models is that targeting processes involved in local invasion (e.g., angiogenesis) can be undertaken at a clinically relevant site (36). Since the early studies showing orthotopic transplantation of colon tumors and metastasis to the liver (39), tumor xenografts have been grown orthotopically in mice. However, despite the clinical relevance of orthotopic models, their utilization is hindered by a need for a high level of technical skill, time and cost. Therapeutic efficacy is also more difficult to assess with orthotopic models in contrast to the relative ease of subcutis tumor measurements (36). 

Killion, J. J, Radinsky, R. and Fidler, I. J. (1999) Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer Metastasis Rev 17, 279-284. 

In these models, tumor cells are typically injected into the flank region where they generally do not form spontaneous metastasis to other tissues (1). In contrast, injecting tumor cells (2) or tumor fragments (3) into orthotopic sites provides a tissue environment more similar to the tissue of origin of the cancer cells and increases the frequency of spontaneous metastasis. Orthotopic models may, therefore, offer a more clinically relevant model to study treatment effects on metastasis, as well as primary tumor growth (4-6). 

An orthotopic model of mCRC with a high rate of metastasis to the para-aortic lymph nodes has been developed utilizing implantation of tumor cells into the submucosal layer of the rectum (11, 12). In these models, primary tumor burden is evaluated by measuring tumor volume with a caliper, while lymph node metastasis is evaluated histologically. 

We have developed a firefly luciferase-expressing HT-29 colorectal cancer cell line, HT-29LP, to realize the benefits of BLI with an orthotopic colorectal cancer model. Primary tumors were established by implantation of HT-29LP cells into the submucosal layer of the rectum of mice, and tumor growth and lymph node metastasis were evaluated. A positive control treatment... 

Establishing Orthotopic HT-29LP Tumors in Nu/Nu Athymic Mice... 

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