Antitumor efficacy of new compounds

Syngeneic mouse models are established with murine cancer cell lines in immuno-competent mice. These models are excellent for studying new antitumor therapeutic agents in the presence of a functional immune system. The C57Bl/6J or Balb/c mouse strains are typically employed to establish the syngeneic model.

Lewis Lung Carcinoma (LLC) growth dynamics in young male C57Bl/6j mice treated with anticancer compounds A, B, and C. 1×10*6 cells in 100 μl (50 μl DMEM+50 μl Matrigel).
LLC tumor microphotographs. Cisplatin and Vehicle-treated. Magnification ×100 (left), ×400 (right). Red arrows indicate diffuse edema, green arrows – mitotic figures, blue arrows – blood vessels, yellow arrows – inflammatory cells, grey arrows – apoptotic cells, asterisks – necrotic loci, triangle – hemorrhage, squares – focal edema.
The number of 4T1 metastases nodules on the lung surface. The data demonstrate individual data points and group medians (middle line). The analysis was performed with the Mann-Whitney test. P-value p < 0.0001 are given with asterisks ****.
Cancer model validation: Orthotopically inoculated DU4475 growth dynamic in SCID/beige and CD1-Foxn1nu 6-7 weeks old females. 2×10*6 Cells in 100 μl (50 μl RPMI+50 μl Matrigel)

Xenograft models utilize human cancer cells that are inoculated into athymic (nude) or severe combined immune deficient (SCID) mice. These xenograft models can be developed as subcutaneous or orthotopic tumors, allowing for the evaluation of drug efficacy specifically against human cancer cells. Our in-house mouse strains include CD1-Foxn1nu and SCID/beige, while other strains are available upon request.

Cancer model validation: The dynamics of individual tumor growth in the SCID/beige after 5×10*6 MDA-MB-231 cell inoculation Cells in 100 μl (50 μl RPMI+50 μl Matrigel). Cells were implanted into the mammary fat pad of 10 weeks old females.

Tumor treatment procedures encompass various routes of drug administration, including invasive methods (IV, IP, SC, and PO), noninvasive methods (via food), and photodynamic therapy (PDT) using a diverse range of irradiation wavelengths.

The deliverable for these studies consists of a comprehensive report that includes the study design, experimental data and interpretation, preliminary statistics, requested tissue samples, and terminal blood samples.

Deliverable: A detailed study report including the description of the study design, experimental data and interpretation, preliminary statistics, requested tissue samples, and terminal blood.

Service details: A standard study design includes 7 days of acclimatization, 5-30 days of tumor growth (depending on cancer cell line type), a study-specific treatment period, and post-treatment observation. A study design includes a minimum of 2 groups of mice (tumor-bearing vehicle-treated and tumor-bearing test compound-treated group). Drug administration can be performed via invasive (IV, IP, SC, and IM routes) or noninvasive (PO, IN, or diet incorporated) routes. Other specific types of treatment are also possible, for example, photodynamic therapy (PDT) using a wide range of irradiation wavelengths. Typically, animals are observed for clinical signs during the treatment and post-treatment periods. The tumor growth dynamic is carefully monitored. A gross necropsy is performed at the endpoint, and metastases are counted. Specific tests, such as hematological, urinary, and blood clinical chemistry analysis, food intake, histopathology, etc., combined with specific endpoints, are available on request. 

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