scholarly journals FEATURES OF EXPRESSION OF CD133 AND CD44 MARKERS OF TUMOR STEM CELLS WITH METASTATIC AND NON-METASTATIC GASTRIC CANCER

2021 ◽  
Vol 20 (1) ◽  
pp. 97-104
Author(s):  
A. B. Sagakyants ◽  
O. I. Kit ◽  
E. P. Ulyanova ◽  
E. Yu. Zlatnik ◽  
I. A. Novikova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Metastatic Gastric Cancer ◽  
Immunohistochemical Method ◽  
Special Role ◽  
Tumor Stem Cells ◽  
Average Percentage ◽  
Tumor Tissues ◽  
Group 2 ◽  
A Prospective Study

Background. Gastric cancer is the second leading cause of cancer-related death due to advanced disease. A special role in the pathogenesis and metastasis of the tumor is assigned to tumor stem cells (TSC ),  responsible for resistance to chemotherapy and radiotherapy and causing tumor progression.Objective: to determine the CD 44 and CD 133 markers of TSC in tumor tissues of non-metastatic and metastatic gastric cancer using the immunohistochemical method.Material and Methods. A prospective study of tumors in patients with gastric cancer was conducted: Group 1 – 20 people with T3–4aN0–3M0G2 tumor, average age 58.9 ± 9.7; Group 2 – 20 people with T3–4aN0–3M1G2 tumor, with metastases in the peritoneum, average age 53.4 ± 11.9. The expression of CD 44 and CD 133 in the tumor tissue was determined by immunohistochemistry.Results. Differences were found in the number of tumor cells expressing the CD 44 marker in the presence and absence of metastases in patients with gastric cancer – their number was 10.0 ± 3.08 and 6.0 ± 2.3, respectively. The CD 133 molecule was detected in 100 % of cases having metastases, while in cases having no metastases, the marker was detected only in 80 % of cases. The average percentage of CD 133 + cells was 21.3 ± 11.6 % in patients with metastatic gastric cancer and 10.0 ± 2.4 % in patients having no metastases.Conclusion. The degree of expression of the CD 44 and CD 133 markers had characteristic differences in patients with gastric cancer, which can be used further to explain the results of the treatment and the prognosis of the disease.

scholarly journals Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽  
2021 ◽  
Vol 40 (12) ◽  
pp. 2296-2308
Author(s):  
Mei Wang ◽  
Xinxin Zhao ◽  
Rong Qiu ◽  
Zheng Gong ◽  
Feng Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Metastatic Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Node Metastasis ◽  
Signaling Activation

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

Expression of CD44 and CD133 in tumor сells of metastatic and non-metastatic gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15531-e15531
Author(s):  
Aleksandr B. Sagakyants ◽  
Oleg I. Kit ◽  
Elena P. Ulianova ◽  
Elena Yu. Zlatnik ◽  
Inna A. Novikova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immunohistochemical Study ◽  
Single Cells ◽  
Chi Square ◽  
Positive Expression ◽  
Tumor Tissues ◽  
Incidence And Mortality ◽  
Chi Square Test ◽  
Group 2 ◽  
Group 1

e15531 Background: High incidence and mortality rates of gastric cancer cause a constant search for the most informative and effective methods of diagnosis and treatment assessment. In this regard, studying the expression of markers with the stem phenotype in primary tumor tissues in patients with gastric cancer with and without metastases is of undoubted interest. Methods: The study included 20 gastric cancer patients aged 30-80 years: group 1 – gastric cancer T3-4аN0-3M0 (G2) without metastasis (58.9±9.7 years); group 2 – gastric cancer T3-4аN0-3M1 (G2) with peritoneal metastasis (53.4±11.9 years). Immunohistochemical study was performed on paraffin-embedded tumor tissue sections using mouse monoclonal antibodies to CD44 (156-3С11 Thermo Scientific) at a 1:2500 dilution and rabbit polyclonal antibodies to CD133 (Cloud-Clone Corp.) at a 1:700 dilution; the Thermo Scientific autostainer was used for staining. Membrane staining and staining intensity were assessed: 0, 1+ weak, 2+ moderate, 3+ strong staining. Positive expression was defined as ≥10% cut-off for CD44 and ˃5% for CD133. Results: Positive expression of CD44+ was detected in 67% (13) in group 2 vs. 20% (4) in group 1. In the metastatic group, the number of cells that stained positive for CD44 expression ranged from 9 to 15%, on average 10.0±3.08%, without metastases – from single cells to 13%, on average 6.0±2.3%. A chi-square test showed statistically significant association in the groups (8.256 at p = 0.004). Positive CD133+ expression in tumor tissues was registered in 100% (20) in group 2 and 80% (16) in group 1. The range of positively stained cells in group 2 was from 10 to 40%, on average 21.3±11.6%, in group 1 - from single cells to 14%, on average 10.0±2.4%. A chi-square test showed statistically significant association in the groups (4.444 at p = 0.036). Conclusions: Immunohistochemical study of the selected tumor cell markers in gastric cancer revealed some characteristics of their expression depending on the presence of metastases. The results can be the basis for further research for the most complete characterization of a heterogeneous tumor population in gastric cancer and the role of individual cells in the tumor growth, progression and metastasis.

scholarly journals CYTOKINE TISSUE PROFILE IN NON-METASTATIC GASTRIC CANCER

2020 ◽  
Vol 66 (5) ◽  
pp. 524-527
Author(s):  
A. Sagakyants ◽  
Oleg Kit ◽  
Ye. Zlatnik ◽  
Ye. Zolotarev ◽  
O. Shulgina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adaptive Immunity ◽  
Tumor Tissue ◽  
Metastatic Gastric Cancer ◽  
Pathological Process ◽  
Special Role ◽  
Functional Elements ◽  
Innate And Adaptive Immunity ◽  
Urgent Task

The development of the tumor process involves the involvement of various functional elements of innate and adaptive immunity. A special role in the reorganization of tissues, changes and evolution of the properties of cancer cells is given to cytokines, the study of the role of which in these processes with various types of neoplasms and, in particular, with nonmetastatic gastric cancer is an urgent task. The aim of the work was to determine the characteristics of the cytokine status in the tissues of patients with non-metastatic gastric cancer. Materials and methods. In the extracts of tumor tissue, perifocal zone, omentum, peritoneum of patients with gastric cancer without metatstases (T3-4aN0-3M0, n = 20, 58.9 ± 9.7 years), the concentration of IL-1P, IL-2, IL -6, IL-8, IL-18, TNF-a, IL-10 and IL-1RA in tumor tissue, the perifocal zone, as well as in the omentum and peritoneum. Results and discussion. In the tumor tissue, an increase in the content of IL-1P, IL-8 and a decrease in IL-2, TNF-a and IL-10 were noted. In the perifocal zone, a decrease in the concentration of IL-1P, IL-6, IL-8 was revealed with an increased content of IL-2, IL-1RA, IL-10, TNF-a and IL-18. Against this background, the omentum and peritoneum compared with the tumor, the concentration of IL-1P, IL-18 and IL-1RA is reduced, against the background of an increase in the concentration of IL-2, IL-6, TNF-a and IL-10. Findings. It was shown that tumor tissue has some features in the cytokine profile compared with unaffected tissues, which can be used to further evaluate the development of the pathological process.

scholarly journals The Expression Pattern of miR-17, -24, -124 and -145 as Diagnostic Factor for Metastatic Gastric Cancer; a Lesson from Gastric Cancer Stem cells

2021 ◽  
Author(s):  
Hamed Yasavoli-Sharahi ◽  
Soheil Jahangiri-Tazehkand ◽  
Zahra Iranmehr ◽  
Changiz Eslahchi ◽  
Amirnader Emami Razavi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Expression Pattern ◽  
Regulatory Networks ◽  
Metastatic Gastric Cancer ◽  
Expression Level ◽  
Metastatic Tumors ◽  
Potential Biomarker ◽  
Gastric Cancer Stem Cells

Background: Distant metastasis of Gastric Cancer (GC) causes more than 700 000 deaths worldwide. Cancer Stem Cells (CSCs) are a subpopulation of cancer cells responsible for aggressiveness and chemoresistance in clinical settings. MicroRNAs (miRNAs) emerge as important players in regulating self-renewal and metastasis in CSCs. Understanding the role of miRNAs in CSCs offer a potential diagnostic tool for GC patients. This study is aimed to identify miRNAs that target both stemness and metastasis in gastric cancer stem cells (GCSCs) and differentially expressed in metastatic GC patients as diagnostic biomarkers for GC metastasis. Methods: We investigate the gene expression profile of patients using the GEO database and Rstudio software. To obtain the regulatory networks and miRNAs, the STRING and miRwalk database used. The gastric cancer tissues were obtained from Iranian National Tumor Bank (INTB) to validate the results. Results: Our results indicated three important regulatory cores affecting the immune system's regulation, tumor progress, and metastasis. Based on the bioinformatics results, four miRNAs miR-17-5p, miR-24-3p, miR-124-3p, and miR-145-5p, were selected, and their expression pattern was evaluated in 10 patients' metastatic tumors compared to 10 nonmetastatic tumors by real-time PCR. The expression level of mir-17, -24, and -124 was upregulated about 8, 10, 60 folds, respectively, and miR-145 was downregulated 4.5 folds in metastatic tumors compared to nonmetastatic tumors. Conclusion: the high expression level of miR-17, -24, -124, and low level of miR-145 in GC patients' samples could be a potential biomarker for the presence of GCSCs and the diagnosis of metastasis.

RISKS OF ANEMIA DEVELOPMENT IN DONORS ACCORDING TO INHERITED PREDISPOSITION AND REGULARITY OF BLOOD DONATION

2020 ◽  
pp. 72-83
Author(s):  
I.M. Vorotnikov ◽  
V.A. Razin ◽  
I.M. Lamzin ◽  
M.N. Sokolova ◽  
M.E. Khapman ◽  
...  
Keyword(s):  
Blood Donors ◽  
Blood Donation ◽  
Hla Antigens ◽  
Hla Typing ◽  
Main Role ◽  
Inherited Predisposition ◽  
Group 2 ◽  
Student’S T ◽  
A Prospective Study ◽  
Group 1

Anemia is one of the most common complications of blood donation. Thus, the objective of the paper was to assess the risks of anemia development in donors according to the regularity of donation and inherited predisposition. Materials and Methods. The authors carried out a prospective study, which included 241 blood donors, using random sampling and case-control techniques. Depending on blood donation frequency, the donors were divided into 2 groups: Group 1 consisted of 122 people (51.5 %) frequently donating blood; Group 2 included 119 people (48. 5 %) rarely donating blood. We studied the initial indicators of a general blood test and the same indicators a year after the first blood donation. Additionally, we performed HLA typing of donors. Statistica v. 8.0 software package (Stat Soft Inc., USA) was used for statistical analysis. To compare two independent samples, we used a nonparametric Mann-Whitney U-test and a parametric Student’s t-test (depending on the type of distribution). To assess anemia risks, the odds ratio was calculated. Results. One year after the first blood donation, anemia was diagnosed in 13 people (10.6 %) in Group 1 and in 7 people (5.9 %) in Group 2 (p=0.179). A11 and B7 HLA antigens did not increase anemia risks in group 1 (OS=1.257 (95 % CI 0.318–4.973) and OS=0.240 (95 % CI 0.051–1.134, respectively). HLA-antigens A11 and B7 did not increase anemia risks in Group 1 (OR=1.257 (95 % CI 0.318-4.973) and OR=0.240 (95 % CI 0.051–1.134), respectively). In group 2, antigen-A11 was also an insignificant factor (OS=2.902 (95 % CI 0.606-13.889)) for anemia development. Whereas, antigen-B7 increased anemia risks by 14 times (OS=14.364 (95 % CI 1.644-124.011)). Conclusion. In rare blood donors, it is the genetic factor that plays the main role in anemia development. High prevalence rates of anemia in frequent blood donors are probably determined by other factors. Keywords: anemia, blood donors, HLA typing. Механизмы развития анемий и факторы, их индуцирующие, остаются до конца не изученными. Целью исследования стало изучение риска развития анемии у доноров крови в зависимости от частоты донации и наличия наследственной предрасположенности к развитию анемии. Материалы и методы. Проведено проспективное исследование, выполненное методами случайной выборки и «случай-контроль», в которое вошел 241 донор крови. В зависимости от частоты сдачи доноры были поделены на 2 группы: группу 1 составили 122 чел. (51,5 %), часто сдающие кровь; группу 2 – 119 чел. (48,5 %), редко сдающих кровь. Изучались исходные показатели общего анализа крови и через год от начала донации. Дополнительно проводилось HLA-типирование доноров. Статистический анализ осуществлялся с применением программы Statistica v. 8.0 (Stat Soft Inc., США). Для сравнения двух независимых выборок использовался непараметрический U-критерий Манна–Уитни и параметрический t-критерий Стьюдента (в зависимости от типа распределения). Для оценки риска возникновения анемии рассчитывалось отношение шансов. Результаты. Через год с момента первой сдачи крови в группе 1 выявлено 13 чел. (10,6 %) с анемией, в группе 2 – 7 чел. (5,9 %) (р=0,179). Наличие HLA-антигенов А11 и B7 не повышало риск развития анемии в группе 1 (ОШ=1,257 (95 % ДИ 0,318–4,973) и ОШ=0,240 (95 % ДИ 0,051–1,134 соответственно). В группе 2 наличие гена А11 также являлось незначимым фактором (ОШ=2,902 (95 % ДИ 0,606–13,889), присутствие гена В7 в 14 раз повышало риск развития анемии (ОШ=14,364 (95 % ДИ 1,664–124,011). Выводы. Высокий риск развития анемии у редко сдающих кровь доноров обусловливается генетическими факторами. Высокая распространённость анемии у часто сдающих кровь доноров, вероятно, определяется другими факторами. Ключевые слова: анемия, доноры крови, HLA-типирование.

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