High rates of cancer incidence and mortality from malignant neoplasms remains an urgent health problem. The development of the most effective therapeutic algorithms is required to improve the survival of cancer patients. An important condition for the discovery of new anticancer drugs and their translation into clinical practice involves the ability to model tumor growth, reproduce the characteristics of human disease, and evaluate measurable effects of pharmacological substances in laboratory facilities. Xenograft models established by direct implantation of fresh tumor tissue samples from individual patients into immunodeficient mice are considered suitable for both preclinical trials and for solving fundamental problems in oncology. The review highlights the significance of patient-derived xenograft models as a platform with high predictive value and the prerequisites that make them the preferred tool for research in cancer biology. The most important methodological aspects in the creation of these models are considered. Methods for obtaining and preparing biological tumor samples for xenotransplantation are discussed. The significance of the immune status, as well as the phenotypic and genetic characteristics of recipient animals, is described. The article presents the limitations of animal models associated with their immunodeficiency status and ways to overcome them. The principles for choosing xenotransplantation sites (heterotopic and orthotopic) and their advantages and disadvantages are discussed. In conclusion, we emphasize the need to continue the work on optimizing PDX (Patient-Derived Xenograft) models to overcome their limitations and to obtain the most reliable and valuable research results in oncology.
As a rule, esophageal adenocarcinoma develops in the lower esophagus. Life expectancy and survival rates depend on the cancer stage and the general health of the patient. Chemoradiotherapy is the most successful treatment approach to this type of cancer. The choice of optimal radiation doses for achieving the best possible therapeutic effect is still a challenge. The aim of this paper was to study effective radiation doses and assess response of human esophageal adenocarcinoma to radiation using a PDX model. The study was conducted in female Balb/c nude mice (n = 25). Fragments of the donor tumor were implanted into the cervical esophagus of immunodeficient mice. Effects of radiation on the obtained orthotopic xenografts were studied after each of 3 irradiation sessions (4, 6, 8, and 10 Gy in each of the experimental groups, respectively). First-passage xenografts reproduced the morphology of the donor tumor. The mean tumor volume differed significantly between the control group and the experimental groups exposed to 6, 8 or 10 Gy (р ≤ 0.01) after each irradiation session. Tumor growth delay was significant after exposure to the total dose of 18 Gy. The further radiation dose increase was ineffective. The reduction of tumor volume in the xenografts was correlated to the increase in the one-time radiation dose. The total dose over 18 Gy produced a detrimental effect on the hematopoietic system and blood biochemistry of the experimental mice.
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