scholarly journals Dynamic Signatures of the Epigenome: Friend or Foe?

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 653 ◽  
Author(s):  
Marta Machnik ◽  
Urszula Oleksiewicz
Keyword(s):  
Tumor Cells ◽  
High Throughput ◽  
Genetic Factors ◽  
Single Gene ◽  
Clonal Diversity ◽  
Evolutionary Adaptation ◽  
Biological Processes ◽  
The Third ◽  
Current Review ◽  
Epigenetic Patterns

Highly dynamic epigenetic signaling is influenced mainly by (micro)environmental stimuli and genetic factors. The exact mechanisms affecting particular epigenomic patterns differ dependently on the context. In the current review, we focus on the causes and effects of the dynamic signatures of the human epigenome as evaluated with the high-throughput profiling data and single-gene approaches. We will discuss three different aspects of phenotypic outcomes occurring as a consequence of epigenetics interplaying with genotype and environment. The first issue is related to the cases of environmental impacts on epigenetic profile, and its adverse and advantageous effects related to human health and evolutionary adaptation. The next topic will present a model of the interwoven co-evolution of genetic and epigenetic patterns exemplified with transposable elements (TEs) and their epigenetic repressors Krüppel-associated box zinc finger proteins (KRAB–ZNFs). The third aspect concentrates on the mitosis-based microevolution that takes place during carcinogenesis, leading to clonal diversity and expansion of tumor cells. The whole picture of epigenome plasticity and its role in distinct biological processes is still incomplete. However, accumulating data define epigenomic dynamics as an essential co-factor driving adaptation at the cellular and inter-species levels with a benefit or disadvantage to the host.

Introduction to GRNs

2010 ◽  
pp. 28-56
Author(s):  
Ugo Ala ◽  
Christian Damasco
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
System Biology ◽  
Regulatory Networks ◽  
New Technologies ◽  
Single Gene ◽  
Biological Processes ◽  
Genome Wide ◽  
Genes Expression ◽  
Organization Analysis

The post-genomic era shifted the main biological focus from ‘single-gene’ to ‘genome-wide’ approaches. High throughput data available from new technologies allowed to get inside main features of gene expression and its regulation and, at the same time, to discover a more complex level of organization. Analysis of this complexity demonstrated the existence of nonrandom and well-defined structures that determine a network of interactions. In the first part of the chapter, we present a functional introduction to mechanisms involved in genes expression regulation, an overview of network theory, and main technologies developed in recent years to analyze biological processes are discussed. In the second part, we review genes regulatory networks and their importance in system biology.

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression

2021 ◽  
pp. 106689692098834
Author(s):  
Raquel Machado-Neves ◽  
Bernardo Teixeira ◽  
Elsa Fonseca ◽  
Pedro Valente ◽  
Joaquim Lindoro ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Tumor Cells ◽  
Rare Case ◽  
Malignant Tumors ◽  
Squamous Cell Carcinomas ◽  
The Third ◽  
The Past ◽  
First Case ◽  
Lymphoplasmacytic Infiltrate

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.

scholarly journals Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Targets ◽  
Clinicopathological Characteristics ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
The Third ◽  
Current Review ◽  
Important Challenge ◽  
Prediction Of Metastasis

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

scholarly journals Arrays of high-aspect ratio microchannels for high-throughput isolation of circulating tumor cells (CTCs)

2013 ◽  
Vol 20 (10-11) ◽  
pp. 1815-1825 ◽  
Author(s):  
Mateusz L. Hupert ◽  
Joshua M. Jackson ◽  
Hong Wang ◽  
Małgorzata A. Witek ◽  
Joyce Kamande ◽  
...  
Keyword(s):  
Aspect Ratio ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Throughput ◽  
High Aspect Ratio

High-throughput concentration of rare malignant tumor cells from large-volume effusions by multistage inertial microfluidics

Lab on a Chip ◽  
2022 ◽  
Author(s):  
Nan Xiang ◽  
Zhonghua Ni
Keyword(s):  
Tumor Cells ◽  
High Throughput ◽  
Malignant Tumor ◽  
Large Volume ◽  
Concentration Factor ◽  
Pleural Effusions ◽  
Inertial Microfluidics ◽  
Low Concentration ◽  
Malignant Pleural Effusions ◽  
On Chip

On-chip concentration of rare malignant tumor cells (MTCs) in malignant pleural effusions (MPEs) with a large volume is challenging. Previous microfluidic concentrators suffer from a low concentration factor (CF) and...

scholarly journals Circulating Tumor Cells and Cancer Stem Cells: Clinical Implications in Nonmetastatic Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40856 ◽  
Author(s):  
M. Sayed ◽  
A.M. Zahran ◽  
M.S.F. Hassan ◽  
D.O. Mohamed
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Overall Survival ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Third ◽  
Disease Free

Purpose Despite the therapeutic advances, disease recurrence remains an ever-present threat to the health and well-being of breast cancer survivors. Assessment of circulating tumor cells (CTCs) and cancer stem cells (CSCs) during and after treatment may be of value in refining treatment. Methods Three 5 mL blood samples were taken from each patient: the first, at diagnosis; the second, after completion of neoadjuvant anthracyclin-based chemotherapy; and the third, a month after surgery and completion of adjuvant radiotherapy. The absolute numbers of CTCs were identified as CD45-cytokeratin+ cells. CTCs per 5 mL of blood were determined by recording all events in the whole suspension. CSCs were identified as cytokeratin+CD44+CD24-/CD45- cells. The CSCs were expressed as a percentage of CTCs. Results Univariate analysis identified the measurements of baseline CTCs and CSCs, taken after chemotherapy and one month after the cessation of radiotherapy, as prognostic factors for both four-year disease-free survival and four-year overall survival. Multivariable analysis identified the third measurement of CSCs, taken one month after the completion of radiotherapy, as the only independent prognostic factor for the four-year disease-free survival (P < 0.002, hazard ratio [HR] = 1.231, 95% CI 1.077–1.407). The initial CTC measurement was the one factor that reached significance on multivariate analysis (P < 0.03, HR 1.969, 95% CI 1.092–3.551) for the four-year overall survival. Correlation was higher between CTC and CSC counts at diagnosis ( r = 0.654, P < 0.001) than after chemotherapy ( r = 0.317, P < 0.03), because of the more rapid decrease in the mean CTC count with chemotherapy. Conclusion The CTC count could be suitable as one of the measures for monitoring response to chemotherapy, while persistence of CSC after cessation of the treatment of nonmetastatic breast cancer, except hormonal therapy when indicated, may be a reason to consider additional therapy in the future. These findings need confirmation in larger randomized trials.

scholarly journals A biolistic method for high-throughput production of transgenic wheat plants with single gene insertions

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Ainur Ismagul ◽  
Nannan Yang ◽  
Elina Maltseva ◽  
Gulnur Iskakova ◽  
Inna Mazonka ◽  
...  
Keyword(s):  
High Throughput ◽  
Single Gene ◽  
Transgenic Wheat ◽  
Biolistic Method

scholarly journals Network Pharmacology to Unveil the Biological Basis of Health-Strengthening Herbal Medicine in Cancer Treatment

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 461 ◽  
Author(s):  
Jiahui Zheng ◽  
Min Wu ◽  
Haiyan Wang ◽  
Shasha Li ◽  
Xin Wang ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Tumor Cells ◽  
High Throughput ◽  
Antigen Processing ◽  
Killer Cell ◽  
Network Pharmacology ◽  
Gene Expressions ◽  
Antitumor Effects ◽  
Biological Basis ◽  
Radix Paeoniae Alba

Health-strengthening (Fu-Zheng) herbs is a representative type of traditional Chinese medicine (TCM) widely used for cancer treatment in China, which is in contrast to pathogen eliminating (Qu-Xie) herbs. However, the commonness in the biological basis of health-strengthening herbs remains to be holistically elucidated. In this study, an innovative high-throughput research strategy integrating computational and experimental methods of network pharmacology was proposed, and 22 health-strengthening herbs were selected for the investigation. Additionally, 25 pathogen-eliminating herbs were included for comparison. First, based on network-based, large-scale target prediction, we analyzed the target profiles of 1446 TCM compounds. Next, the actions of 166 compounds on 420 antitumor or immune-related genes were measured using a unique high-throughput screening strategy by high-throughput sequencing, referred to as HTS2. Furthermore, the structural information and the antitumor activity of the compounds in health-strengthening and pathogen-eliminating herbs were compared. Using network pharmacology analysis, we discovered that: (1) Functionally, the predicted targets of compounds from health strengthening herbs were enriched in both immune-related and antitumor pathways, similar to those of pathogen eliminating herbs. As a case study, galloylpaeoniflorin, a compound in a health strengthening herb Radix Paeoniae Alba (Bai Shao), was found to exert antitumor effects both in vivo and in vitro. Yet the inhibitory effects of the compounds from pathogen eliminating herbs on tumor cells proliferation as a whole were significantly stronger than those in health-strengthening herbs (p < 0.001). Moreover, the percentage of assay compounds in health-strengthening herbs with the predicted targets enriched in the immune-related pathways (e.g., natural killer cell mediated cytotoxicity and antigen processing and presentation) were significantly higher than that in pathogen-eliminating herbs (p < 0.05). This finding was supported by the immune-enhancing effects of a group of compounds from health-strengthening herbs indicated by differentially expressed genes in the HTS2 results. (2) Compounds in the same herb may exhibit the same or distinguished mechanisms in cancer treatment, which was demonstrated as the compounds influence pathway gene expressions in the same or opposite directions. For example, acetyl ursolic acid and specnuezhenide in a health-strengthening herb Fructus Ligustri lucidi (Nv Zhen Zi) both upregulated gene expressions in T cell receptor signaling pathway. Together, this study suggested greater potentials in tumor immune microenvironment regulation and tumor prevention than in direct killing tumor cells of health-strengthening herbs generally, and provided a systematic strategy for unveiling the commonness in the biological basis of health-strengthening herbs in cancer treatment.

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

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