Experimental oncology最新文献

The aim of the study was to determine the association of indicators of the progression of endometrioid carcinoma of the endometrium (ECE) with the type of stromal microenvironment, the counts of CXCL12+ fibroblasts and CD163+ macrophages, and the expression of the chemokine CXCL12 and its receptor CXCR4 in tumor cells.

Materials and methods: Histological preparations of ECE samples (n = 51) were analyzed. Expression of CXCL2 and CXCR4 antigens in tumor cells, the content of CXCL12+ fibroblasts and CD163+ macrophages, and the density of microvessels were determined by the immunohistochemical method.

Results: Groups of ECE with desmoplastic and inflammatory stromal reactions were delineated. The majority (80.0%) of tumors with desmoplasia were of low differentiation grade, deeply invading the myometrium; 65.0% of patients with these tumors were at stage III of the disease. In ECE cases of stages I-II, 77.4% of ECE showed an inflammatory type of stroma. The high angiogenic and invasive potential of EC of stages I-II was associated with an inflammatory stromal type, high counts of CD163+ macrophages and CXCL12+ fibroblasts in the tumor microenvironment, high expression of the chemokine receptor CXCR4, and reduced expression of its ligand CXCL12 in tumor cells. In the majority of EC of stage III, the increase in angiogenic, invasive, and metastatic potential was accompanied by the presence of desmoplastic stroma, increased expression of CXCR4 in tumor cells, and a high count of CXCL12+ fibroblasts.

Conclusions: The obtained results showed that the morphological architecture of the stromal ECE component is related to the molecular features of its constituents and tumor cells. Their interaction modulates the phenotypic characteristics of ECE associated with the degree of malignancy.

Background: Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling.

Aim: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC.

Materials and methods: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients.

Results: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes.

Conclusion: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.

Background: HGF/c-Met is one of the main signaling pathways that ensure communication between epithelial cells and components of the tumor microenvironment determining the invasive and metastatic potential of many cancers. However, the significance of HGF and c-Met in endometrial carcinoma (ECa) progression remains unclear.

Aim: To evaluate copy number variations as well as expression of the c-Met receptor and its ligand HGF in endometrial carcinomas considering the clinical and morphological characteristics of ECa.

Materials and methods: The study was conducted on ECa samples of 57 patients, among which 32 had lymph nodes and/or distant metastasis. The copy number of c-MET gene was estimated by qPCR. The expression of HGF and c-Met in tissue samples was determined by the immunohistochemical method.

Results: Amplification of c-MET gene was detected in 10.5% of the ECa cases. In most carcinomas, a combined expression pattern of HGF and c-Met was established, in which co-expression of these markers was observed in tumor cells, and the content of HGF+ fibroblasts increased in the stroma. The expression of HGF in tumor cells was associated with the tumor differentiation grade and was higher in G3 ECa (p = 0.041). The number of HGF+ fibroblasts in the stromal component increased in the ECa cases with metastasis compared to the cases without metastasis (p = 0.032). The content of stromal c-Met+ fibroblasts was higher in deeply invasive carcinomas of patients with metastases than in tumors with invasion of < 1/2 myometrium (p = 0.035).

Conclusion: Increased expression of HGF and c-Met in stromal fibroblasts of endometrial carcinomas is associated with metastasis in patients with ECa and deep invasion of the tumor into the myometrium, and can contribute to the aggressive course of the disease.

Studying the biological characteristics of bladder cancer in primary culture can be an effective way for diagnostic and prognostic purposes, as well as choosing a scheme for personalized therapy.

Aim: To characterize and compare 2D and 3D primary cell cultures obtained from the same tumor sample resected from a patient with high-grade bladder cancer.

Materials and methods: 2D and 3D primary cell cultures were obtained from explants of resected bladder cancer. Glucose metabolism, lactate dehydrogenase (LDH) activity, and level of apoptosis were studied.

Results: Multicellular tumor spheroids (3D) differ from planar culture (2D) by more pronounced consumption of glucose from the culture medium (1.7 times higher than 2D on Day 3 of culture), increased lactate dehydrogenase activity (2.5 times higher on Day 3 vs. Day 1 of cultivation, while in 2D culture LDH activity is constant), stronger acidification of the extracellular environment (pH dropped by 1 in 3D and by 0.5 in 2D). Spheroids demonstrate enhanced resistance to apoptosis (1.4 times higher).

Conclusion: This methodological technique can be used both for tumor characterization and for selection of optimal postoperative chemotherapeutic schemes.

Aim: To improve the diagnostics of lymphogenic metastasis in patients with rectal cancer (RCa) by combining magnetic resonance imaging (MRI) with the blood carcinoembryonic antigen (CEA) level assessment.

Materials and methods: We have systematized and analyzed the results of the examination and treatment of 77 patients with stage II-III rectal adenocarcinoma (T2-3N0-2M0). Before the start of neoadjuvant treatment as well as 8 weeks after its completion, computed tomography (CT) and MRI were performed. We analyzed such prognostic criteria as the size, shape, and structure of lymph nodes as well as the patterns of contrast accumulation. As a prognostic marker, CEA levels in the blood of patients with RCa before surgical treatment were assessed.

Results: Radiological exams showed a rounded shape and heterogeneous structure to be the most informative for predicting metastatic lymph node damage, increasing the probability by 4.39 and 4.98 times, respectively. After neoadjuvant treatment, the percentage of positive histopathological reports on lymph node involvement decreased significantly to 21.6% (р ˂ 0.001). MRI showed 76% sensitivity and 48% specificity for assessing lymphogenic metastasis. CEA levels differed significantly between stages II and III (N1-2) (р ˂ 0.032) with a threshold value of 3.95 ng/ml.

Conclusions: In order to increase the effectiveness of the diagnosis of lymphogenic metastasis using radiological examination methods in RCa patients, such prognostic criteria as the round shape and heterogeneous structure of the lymph nodes and the threshold level of CEA should be considered.

Background: The neutrophil-to-lymphocyte ratio (NLR) turned out to be a routinely available marker capable to reflect the systemic inflammatory response created by a tumor. Gastric cancer (GC) grows in the anatomical vicinity of adipose tissue, which is also associated with low-grade inflammation.

Aim: To investigate the usefulness of the combined use of preoperative NLR and density of intratumoral cancer-associated adipocytes (CAAs) for predicting the disease outcome in GC patients.

Materials and methods: A total of 151 patients with GC were eligible for retrospective analysis between 2009 and 2015.NLR preoperative values were calculated. Perilipin expression in tumor tissue was examined immunohistochemically.

Results: Low preoperative NLR is the most reliable prognostic factor for the favorable outcome for patients with low density of intratumoral CAAs. Patients with a high density of CCAs are at high risk of lethal outcomes independently of the value of preoperative NLR.

Conclusion: The results have clearly shown an association between preoperative NLR and the density of CAAs in the primary tumor of GC patients. The prognostic value of NLR is essentially modified by means of the individual density of intratumoral CAAs in GC patients.The elevated NLR could be of significant predictive potential for a negative prognosis for patients with tumors characterized by the high density of CAAs independently of BMI.

Background: Despite the large number of studies devoted to the study of the features of tumor microenvironment in breast cancer (BCa), presently there is no consensus on the features of MMP-2 and MMP-9 expression in the tumor tissue of BCa patients depending on the age. The aim of the study was to investigate the relationship between MMP-2 and -9 expression at the protein and mRNA levels in BCa tissues and the clinical and pathological features of BCapatientsin different age groups.

Materials and methods: The expression level of MMP-2 and -9in the BCa tissue of patients of two age groups (< 45 years and > 45 years) was studied using the bioinformatics method (UALCAN database), immunohistochemical method, and real-time PCR.

Results: It was established that a characteristic feature of BCa in young patients is the low level of MMP2 mRNA against the background of increased expression of this gelatinase at the protein level, as well as decreased expression of MMP9 at both the mRNA and protein levels. When analyzing the correlation of the gelatinase expression indices in BCa tissue of young patients, depending on the clinical and pathological features, a significantly lower level of MMP-2 expression was recorded in BCa cases of stage II compared to the indices of stage I cases. High expression of MMP-2 and -9 was recorded in BCa tissue in node-positive cases and the basal molecular BCa subtype.

Conclusions: The identified relationship between the expression of the studied gelatinases and such indices of BCa malignancy as its stage, positive regional lymph node status, and the molecular BCa subtype in young patients indicates the need for further research of the features of the tumor microenvironment to predict the cancer aggressiveness.

Background: Locally advanced breast cancer (LABC) rates are unusually high in developing countries. There is a need for the identification of predictive biomarkers for the selection of patients who could benefit from neoadjuvant chemotherapy (NAC).

Aim: As the expression of ALU repeat is increased in cancer and has not been assessed in liquid biopsy of cancer patients, our goal was to assess ALU expression in the blood plasma of LABC patients during NAC.

Patients and methods: Plasma samples drawn at baseline and at the end of the fourth cycle of chemotherapy were used to determine the plasma levels of ALU-RNA by quantitative real-time PCR.

Results: ALU expression from baseline to the fourth cycle of NAC increased from a median relative level of 1870 to 3370 in the whole group (p = 0.03). The increase in ALU-RNA levels in the course of NAC was more pronounced in premenopausal women and in patients with hormone-positive tumors. In patients with complete response to NAC, baseline ALU expression was higher than that in those with partial response.

Conclusion: This exploratory study provides evidence that plasma ALU-RNA levels are modulated by the menopausal status and hormone receptor status of breast cancer patients and pre-therapeutic ALU-RNA levels might be useful in predicting the response to chemotherapy in a neoadjuvant setting.

Aim: To study the expression of the programmed cell death receptor (PD-1) and its ligand (PD-L1) by immunocompetent cells in endometrial cancer patients with metabolic disorders.

Materials and methods: Populations and subpopulations of lymphocytes were analyzed by flow cytometry. Antibodies against CD279 were used to detect PD-1 on the CD4+ and CD8+ T cells. Antibodies against CD14 and CD274 were used to detect PD-L1 on monocytes.

Results: In patients with severe metabolic disorders, the expression of PD-1 on CD8+ and CD4+ lymphocytes and the expression of the corresponding PD-L1 on CD14+ cells before treatment and after radiation therapy were higher than in the control group.

Conclusion: Theincreased expression of PD-1 and PD-L1 receptors by immunocompetent cells can be considered a new prognostic marker in endometrial cancer patients with morbid obesity.

Background: Familial non-medullary thyroid carcinoma (FNMTC) is defined as cancer developing in two or more first-degree relatives if predisposing factors, for example, radiation, are absent. The disease can be either syndromic, when it is a component of complex genetic syndromes, or non-syndromic (95% cases). The genetic basis of non-syndromic FNMTC is unknown; the clinical behavior of tumorsis unclear and, at times, contradictory.

Aim: To analyze clinical manifestations of FNMTC and compare them with the data for sporadic papillary thyroid carcinomas in patients of the same age groups.

Materials and methods: We examined 22 patients (a "parents" group and a "children" group) suffering from the non-syndromic FNMTC. For comparison, two groups of sporadic papillary carcinomas patients of the same age were drawn up("adult" and "young"). We analyzed tumor size and frequency of the distributionby the categoryof TNM system, invasiveness, multifocality, metastases to lymph nodes, type and extent of surgical and radioiodine treatment, and prognosis according to the MACIS criterion.

Results: Whether sporadic or familial, the tumor size, metastatic potential, and invasive potential are higher in young people, asalready known. There was no significant difference between the "parents" and "adult" groups of patients in terms of tumor parameters. One exception was the higher frequency of multifocal tumors in the FNMTC patients. Meanwhile, compared to the "young" sporadic papillary carcinomas patients, the FNMTC "children" had a higher frequency of T2 tumors, metastasizing (N1a-N1ab), and multifocal tumors, but a lower frequency of carcinomas with intrathyroidal invasions.In the FNMTC "children" compared to FNMTC "parents" was a higher frequency of T2 tumors, metastasizing carcinomas, and tumors with capsular invasion.

Conclusion: FNMTC carcinomas are more aggressive than sporadic ones, especially in patients who are first-degree relatives in a family with parents already diagnosed with the disease.