scholarly journals Molecular determinants of recurrences of the human urothelial tumor

2021 ◽  
Vol 17 (3) ◽  
pp. 130-139
Author(s):  
V. Yu. Startsev ◽  
A. E. Balashov ◽  
A. S. Merzlyakov ◽  
S. L. Vorobiov ◽  
E. S. Kozorezova
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Urothelial Carcinoma ◽  
Expression Profiles ◽  
Transitional Cell ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Clinical Diagnostics ◽  
Tumor Focus ◽  
Tumor Dna

Background. Urothelial carcinoma (UTC) is an aggressive disease with a known propensity for frequent recurrence. It is difficult to predict the velocity of the development of UTC recur using modern means of clinical diagnostics. Therefore, the development of the capabilities of histo-morphological study of tumor tissues is of particular relevance.Materials and methods. The materials of publications (PubMed, CrossRef) for 1990-2021, devoted to the choice of biomarkers for the diagnosis of UTC, the analysis of molecular pathways, progression and metastasis, were studied. The search was carried out for the key phrases "urothelial carcinoma", "recurrent UTK", "stem cells", "biomarkers of bladder cancer", "genetic changes in urothelium", "circulating tumor DNA".Results. Cancer stem cells serve as a source of UTC recurrence after removal from the primary focus, localizing in any areas of the urothelium, as well as outside the main tumor focus and are characterized by a common genotype, but different phenotypic manifestations. To predict the recurrence of the tumour is advisable to use gene expression signatures, since the subtypes of UTC are characterized by clear gene expression profiles. A larger sample and independent dataset is needed to confirm the clinical significance of the findings. Combined biomarkers predict UTC behavior, and FGFR3 and TP53 mutations can be components for a panel for predicting UTC recurrence. The use of the liquid biopsy method with the determination of the level of circulating tumor DNA is a promising diagnostic method that needs to evaluate the results of an initiated randomized trial.Conclusion. The accumulation of knowledge base about the molecular patterns of UTC will help bridge the gap between the results of molecular genetic and clinical diagnostics. Molecular changes in the transitional cell UTC demonstrates a high potential for determining the timing of tumor recurrence, assessing disease-free survival of patients and for planning the resource base of the healthcare system.

scholarly journals Circulating tumor DNA as a prognostic marker in high-risk endometrial cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weiwei Feng ◽  
Nan Jia ◽  
Haining Jiao ◽  
Jun Chen ◽  
Yan Chen ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Tumor Recurrence ◽  
Disease Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Samples ◽  
Free Survival ◽  
Tumor Relapse ◽  
Disease Free ◽  
Tumor Dna

Abstract Background Currently, there is no reliable blood-based marker to track tumor recurrence in endometrial cancer (EC) patients. Liquid biopsies, specifically, circulating tumor DNA (ctDNA) analysis emerged as a way to monitor tumor metastasis. The objective of this study was to examine the feasibility of ctDNA in recurrence surveillance and prognostic evaluation of high-risk EC. Methods Tumor tissues from nine high-risk EC patients were collected during primary surgery and tumor DNA was subjected to next generation sequencing to obtain the initial mutation spectrum using a 78 cancer-associated gene panel. Baseline and serial post-operative plasma samples were collected and droplet digital PCR (ddPCR) assays for patient-specific mutations were developed to track the mutations in the ctDNA in serial plasma samples. Log-rank test was used to assess the association between detection of ctDNA before or after surgery and disease-free survival. Results Somatic mutations were identified in all of the cases. The most frequent mutated genes were PTEN, FAT4, ARID1A, TP53, ZFHX3, ATM, and FBXW7. For each patient, personalized ddPCR assays were designed for one-to-three high-frequent mutations. DdPCR analysis and tumor panel sequencing had a high level of agreement in the assessment of the mutant allele fractions in baseline tumor tissue DNA. CtDNA was detected in 67% (6 of 9) of baseline plasma samples, which was not predictive of disease-free survival (DFS). CtDNA was detected in serial post-operative plasma samples (ctDNA tracking) of 44% (4 of 9) of the patients, which predicted tumor relapse. The DFS was a median of 9 months (ctDNA detected) versus median DFS undefined (ctDNA not detected), with a hazard ratio of 17.43 (95% CI, 1.616–188.3). The sensitivity of post-operative ctDNA detection in estimating tumor relapse was 100% and specificity was 83.3%, which was superior to CA125 or HE4. Conclusions Personalized ctDNA detection was effective and stable for high-risk EC. CtDNA tracking in post-operative plasma is valuable for predicting tumor recurrence.

scholarly journals Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Fatemeh Khodabandehloo ◽  
Sara Taleahmad ◽  
Reza Aflatoonian ◽  
Farzad Rajaei ◽  
Zahra Zandieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Wnt Signaling Pathway ◽  
Hub Genes ◽  
Gene Expressions ◽  
Cell Based Therapy ◽  
Wnt Pathways ◽  
Key Pathways

Abstract Background Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT.

scholarly journals Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D Collagen Scaffolds

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Expression Profiles ◽  
Three Dimensional ◽  
Uniaxial Tensile ◽  
Adipose Derived Stem Cells ◽  
Collagen Scaffolds ◽  
Differentiation Potential ◽  
Tenogenic Differentiation ◽  
Matrix Organization

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.

Gene Expression Regulation underlying Osteo-, Adipo-, and Chondro-Genic Lineage Commitment of Human Mesenchymal Stem Cells

2013 ◽  
pp. 76-94 ◽  
Author(s):  
Ana M. Sotoca ◽  
Michael Weber ◽  
Everardus J. J. van Zoelen
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Expression Regulation ◽  
Expression Profiles ◽  
Human Mesenchymal Stem Cells ◽  
Gene Expression Profiles ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Lineage Commitment

Human mesenchymal stem cells have a high potential in regenerative medicine. They can be isolated from a variety of adult tissues, including bone marrow, and can be differentiated into multiple cell types of the mesodermal lineage, including adipocytes, osteocytes, and chondrocytes. Stem cell differentiation is controlled by a process of interacting lineage-specific and multipotent genes. In this chapter, the authors use full genome microarrays to explore gene expression profiles in the process of Osteo-, Adipo-, and Chondro-Genic lineage commitment of human mesenchymal stem cells.

scholarly journals Increased circulating tumor DNA as a noninvasive biomarker of early treatment response in patients with metastatic ovarian carcinoma: A pilot study

Tumor Biology ◽  
2020 ◽  
Vol 42 (5) ◽  
pp. 101042832091919 ◽  
Author(s):  
Mariana Cartaxo Alves ◽  
Fernando Luiz Affonso Fonseca ◽  
Alayne Magalhães Trindade Domingues Yamada ◽  
Lílian Arruda do Rego Barros ◽  
André Lopes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Early Response ◽  
Circulating Tumor Dna ◽  
Free Survival ◽  
Disease Free ◽  
Tumor Dna

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.

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