The influence of tumor sampling topology on the effectiveness of the xenotransplantation procedure in the creation of a PDX model of gastric cancer

As indicated in the extant literature, numerous research groups encounter challenges in creating PDX models of gastric cancer, which is associated with a low level of engraftment of tumor samples. Consequently, in the pursuit of enhancing and refining the conventional implantation technique, we have recognized the significance of the tumor sample collection site. It was hypothesized that cells located on the tumor periphery and forming the invasion front may have a more prjonounced potential for malignant growth and, consequently, the ability to grow as xenografts. To this end, ten gastric tumor samples were obtained from each patient: five from the tumor edges and five more from areas more than 5 mm from the visible tumor edge. All samples were implanted subcutaneously on the right side of Balb/C Nude mice. A subsequent analysis of the results indicated that, upon the collection of biological material concurrжent with the capture of the visible tumor edge, the formation of tumor nodules occurred in three out of five recipient animals. Consequently, the xenotransplantation efficiency in this instance was determined to be 84%. Conversely, when tissue samples were obtained from areas distant from the tumor edge, the formation of tumor nodules in recipient animals was observed in only one procedure out of five. Consequently, the xenotransplantation efficiency was 20%. The histological examination conducted as part of this study revealed that the heterotopic PDXs accurately reproduced the histotype of the corresponding donor tumors, confirming their adenocarcinoma status. We also conducted an IHC study, which demonstrated that the level of Ki-67 expression in the tumor edges forming the invasion front was significantly higher, with an average value of 70 [60; 80]%. Conversely, in samples extracted from non-marginal regions of the same tumor, Ki-67 expression levels were notably lower, with an average of 15% [5; 25%] (p<0.05). The obtained data suggest that the higher proliferative potential characterizing the marginal areas of tumors may contribute to more effective xenotransplantation of such tumor samples compared to samples obtained from areas of the tumor remote from the visible edge and characterized by a lower proliferative potential.

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