The aim of the study was to carry out a comparative morphological and immunohistochemical analysis of peripheral non-small cell lung cancer, which served as a source of a xenograft tumor, and tissues of the third generation of a tumor that developed in animals.Material and methods. We used 19 athymic BALB/c nu/nu mice, which were intraperitoneally injected with 1×106 CD8+ after sublethal irradiation in accordance with the humanization protocol. The transplantation of a tumor obtained from a 64-year-old patient was carried out three times consecutively. Samples of the original and xenograft tumors were automatically stained with hematoxylin and eosin, rabbit anti-CK7, anti-TTF, and anti-Ki67 antibodies. The evaluation of histological samples was carried out in accordance with the WHO recommendations (2015).Results. It has been established that a third-generation tumor developing in the body of athymic humanized mice retains the morphological and immunohistochemical features of the patient's original tumor. The described approach may be used in preclinical and personalized studies in fundamental pharmacology and molecular oncology.

Introduction. Non-small cell lung cancer (NSCLC), including squamous cell carcinoma, accounts for 80% of all lung cancers. Anti-angiogenic drugs are currently available for NSCLC treatment. However, there are no predictive biomarkers for selecting patients who could benefit from this therapy. The aim of the study was to assess the correlation between the density of the tumor vascular microenvironment and the tumor size, as well as between the density of tumor lymphatic vessels and the presence or absence of metastases in the ipsilateral peribronchial lymph nodes. Materials and methods. Patients with a morphologically verified diagnosis of squamous cell lung carcinoma were divided into 2 groups depending on the stage of cancer: group 1 (stage I, n=15) and group 2 (stage II, n=15). We performed a morphometric study of histological slides stained with hematoxylin and eosin and antibodies to CD34 and Podoplanin (specific and sensitive markers to blood and lymphatic vessels, re-spectively) with immunohistochemical methods. Vascular density was assessed according to the Chalkley method. We quantitatively evaluated the density of blood vessels in absolute numbers on a 0.73-mm² area with a magnification of ×200 (three fields of view were evaluated with subsequent calculation of the mean blood vessels density). Results. The median of vascular density of the microvasculature was 9.67 (8.67; 10.33) and 10.33 (9.67; 11.67) in the intratumoral zone in group 1 and group 2, respectively. In the peritumoral zone, it was 12 (11.33; 12.67) for group 1 and 16.33 (15.67; 19.67) for group 2. The median density of lymphatic vessels in group 1 and group 2 in the intratumoral zone amounted to 1.5 (1; 2) and 2 (1.67; 3.75), respectively; whereas in the peritumoral zone, this parameter was 2 (1.92; 2.75) and 3.33 (2.67; 4) for groups 1 and 2, respectively. We found a correlation between tumor size and vascular density of the microvasculature in the peritumoral zone (p<0.05) and between the density of lymphatic vessels in the peritumoral zone and the presence of metastases in the peribronchial lymph nodes (p<0.05). Conclusion. Features of the vascular microenvironment of the tumor contribute to the progression of squa-mous cell carcinoma of the lung. Keywords: squamous cell lung cancer, tumor vascular microenvironment, tumor vascular density

No abstract

The work studied the antitumor activity of a new compound, a pyridine derivative LHT-13-19. To determine the effective inhibitory concentration, a culture of human colon cancer HCT116 was used. Incubation of tumor cells was carried out in the presence of LHT-13-19 in the concentration range from 10-9 to 10-7 M. The survival of tumor cells was determined in MTT test. In vivo experiments were performed on thirty athymic humanized 12-week-old female BALB/c nu/nu mice with xenograft colorectal adenocarcinoma. All animals were divided into 3 groups, 10 mice in each: animals of the control group were injected daily intraperitoneally with 0.5 ml of PBS, animals of the second group were treated with a cyclophosphamide at a dose of 10 mg/kg, mice of the third the groups received LHT-13-19 as experimental therapy at a daily dose of 3.7 mg/kg during 10 days. Animals’ survival and antitumor activity were assessed. Tumor-doubling time, the number of liver superficial metastases and survival time were estimated. Daily incubation of human colon tumor cells with LHT-13-19 is accompanied by the formation of the cytotoxic effect of the compound. On a xenograft model of colon adenocarcinoma in humanized BALB/c nu/nu mice, a 10-day course of 3.7 mg/kg LHT-13-19 leads to the formation of an antitumor effect due to increase in the time of tumor doubling, animal survival and a decrease in the frequency of metastasis