We aimed to investigate the relationship between the degree of mast cells' (MCs) infiltration and clinicopathological features of prostate cancer (PCa) malignancy and to find out the possible mechanisms of the involvement of these cells in the formation of the aggressive course of the PCa development. The study was conducted on the clinical material of 60 patients with PCa of stages II-III. MCs in the PCa tissue were determined by a histochemical method using toluidine blue. The expression of osteopontin (OPN) was studied by the immunohistochemical method. The expression of miRNA-21, -126, -146a, -181a, and -221 was investigated by quantitative real-time PCR. Statistical processing of the results was performed using the GraphPad Prism 8 program. Our results demonstrated that the increased level of infiltration and degranulation of MCs in the PCa tissue was associated with such indices of the malignancy of the tumor process as the Gleason score and the preoperative PSA level in the blood serum of patients. A high level of MCs infiltration of the PCa tissue was associated with a significant decrease in the two-year recurrence-free survival rates of the patients by 23.3% (р=0.0455). A high degree of MCs infiltration of the PCa tissue was associated with 1.2 times (p=0.0347) higher level of OPN expression and 1.7 (p=0.0051) and 1.65 (p=0.0087) times lower levels of miR-126 and miR-181a expression, respectively. The obtained results indicate the participation of MCs as a factor of the tumor microenvironment in the PCa progression.
The changes in the quantitative parameters and spatial structure of collagen are considered a key diagnostic and prognostic factor associated with the development of many malignant neoplasms, including breast cancer (BCa). The aim of the work was to develop and test an algorithm for the assessment of collagen organization parameters as informative attributes associated with BCa for developing technology of machine learning and building an intelligent system of cancer diagnostics. Materials and Methods: Tumor tissue samples of 5 patients with breast fibroadenomas and 20 patients with stage I–II BCa were studied. Collagen was identified histochemically by Mallory method. Photomicrographs of the studied preparations were obtained using a digital microscopy complex AxioScope A1. Morphometric studies were performed using the software CurveAlign v. 4.0. beta and ImageJ. Results: The algorithm for determining the quantitative characteristics and spatial organization of the collagen matrix in tumor tissue samples has been developed and tested. We showed that collagen fibers in the BCa tissue are characterized by significantly lower values of length (p < 0.001) and width (p < 0.001) as well as higher values of straightness (p < 0.001) and angle (p < 0.05) compared to these in the fibroadenoma tissue. No significant difference was found in the density of collagen fibers in the tissue of benign and malignant neoplasms of the mammary gland. Conclusion: The algorithm allows assessing a wide range of parameters of collagen fibers in tumor tissue, including their spatial orientation and mutual arrangement, parametric characteristics and density of the three-dimensional fibrillar network.
The aim of the study was to compare the expression of markers of bone remodeling in vitro in breast cancer (BCa) cells and prostate cancer (PCa) cells varying in their malignancy phenotype. Materials and Methods: The study was performed on human BCa cells (MCF-7 and MDA-MB-231 lines) and PCa cells (LNCaP and DU-145 lines). Expression levels of bone tissue remodeling proteins (osteopontin (OPN), osteonectin (ON) and bone morphogenetic protein 7 (BMP-7) were determined immunocytochemically. The mRNA levels of bone tissue remodeling proteins OPN (SPP1), ON (SPARC), BMP-7 (BMP7)) and miRNA-10b, -27a, -29b, -145, -146a were assessed by quantitative reverse transcription polymerase chain reaction. To search for miRNAs involved in the regulation of target genes, miRNet v. 2.0 resource was used. Results: We have shown that highly malignant MDA-MB-231 cells are characterized by significantly higher expression of OPN and ON on the background of decreased SPARC and BMP7 mRNA expression. In highly malignant DU-145 cells, ON and SPP1, SPARC, and BMP7 mRNA expression was significantly higher compared with low malignant LNCaP cells. MDA-MB-231 line was characterized by significantly higher expression of miRNA-10b, -27a, -29b, -145 and -146a. In DU-145 cells, significantly lower levels of expression of miRNAs-27a and -145 against the background of increasing levels of miRNAs-29b and -146a were recorded. Conclusion: High malignancy phenotype of the BCa and PCa cells is characterized by high levels of expression of bone remodeling proteins, which may be caused by impaired regulation of their expression at the epigenetic level.
Gastric and colorectal cancer models are essential for the advancement of precision medicine discovery and development. 2D attached monolayer, spheroid and organoid approaches have all been used in the formation of biobanks containing primary patient-derived cells. Here, we report an assessment of those procedures for a panel of nine patient-derived adenocarcinoma samples, along with the most applicable method for the bio-banking of these cell types. A live cell biobank of tumour specimens would facilitate drug discovery laboratories to evaluate drugs on the population of cell cultures, prior to the clinical phase.
Summary. Aim: to determine at the optical level the role of the fibrillar organization of the collagen-containing connective tissue component of the primary tumor focus in prostate cancer (PCa) progression. Objects and methods: the morphological study is based on the analysis of the histological material of the primary tumor foci of 55 PCa patients without tumor progression in the postoperative period and bone metastases. The tumors were graded Gleason 6–9 at surgery. The features of the architecture of collagen-containing connective tissue in tumors were determined in histological slides stained by Van-Gieson. Results: the remodeling of the collagen-containing stromal component located both around the glandular structures (increase in the percentage of straight and aligned collagen fibers compared to the curved ones) and in the stroma itself has been found. Such remodeling is manifested by an increase in the total mass of fibrous structures, an increase in the width of collagen fibrils, their compaction in relation to the density of their location, peculiarities of desmoplasia, alignment and elongation. The specified features are consistent with the Gleason score and the postoperative disease course, namely, the occurrence of metastases. Conclusions: the desmoplastically changed collagen-containing connective tissue component of the PCa creates favorable conditions for the unimpeded migration and realization of the invasive potential of cancer cells, in particular those expressing bone tissue remodeling proteins.
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