scholarly journals Telomere and Centromere Staining Followed by M-FISH Improves Diagnosis of Chromosomal Instability and Its Clinical Utility

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 475 ◽  
Author(s):  
Radhia M’kacher ◽  
Bruno Colicchio ◽  
Claire Borie ◽  
Steffen Junker ◽  
Valentine Marquet ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Chromosomal Instability ◽  
Fish Analysis ◽  
Telomere Dysfunction ◽  
Genetic Syndromes ◽  
Genetic Syndrome ◽  
Dicentric Chromosomes ◽  
Telomere Loss ◽  
Conventional Cytogenetics

Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogenetics. We ascribe this discrepancy to the identification of the unique configuration of dicentric chromosomes. We observed significantly higher frequencies of telomere loss and deletion in patients with dicentric chromosomes (p < 10−4). TC+M-FISH analysis is superior to classical cytogenetics for the detection of chromosomal instability. Our approach is a relatively simple but useful tool for documenting telomere dysfunction and chromosomal instability with the potential to become a standard additional diagnostic tool in medical genetics and the clinic.

Chromosomal Instability Induced by Overexpression of Telomere Repeats Binding Factor 1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4398-4398
Author(s):  
Jianping Lan ◽  
He Huang ◽  
Yuanyuan Zhu ◽  
Jian Yu ◽  
Jie Sun
Keyword(s):  
Telomere Length ◽  
Chromosomal Instability ◽  
Negative Regulator ◽  
Stable Cell Line ◽  
Telomere Dysfunction ◽  
Dicentric Chromosomes ◽  
Cycle Arrest ◽  
Binding Factor ◽  
Lagging Chromosome ◽  
Elevated Frequency

Abstract Telomere dysfunction has been associated with chromosomal stability in process of oncogenesis. Telomere, a special nucleoprotein complex at the termini of linear eukaryotic chromosomes, functions to prevent chromosomes from degradation by endogenous nucleases, fusion and recombination of chromosome ends, triggering DNA damage response and checkpoint-induced cell cycle arrest or apoptosis. Telomere homoeostasis and length are maintained by a set of telomere binding proteins. Among these, telomere repeats binding factor 1(TRF1) serves as a negative regulator of telomere length since TRF1 overexpression would elicit the shortening of telomere length in telomerase-positive cells. To date, the expression level of TRF1 in human cancers remains controversial and its role and mechanism in tumorigenesis are poorly understood. To answer these questions, we introduced EGFP-tagged TRF1 plasmid into HeLa cells to establish a stable cell line with TRF1 overexpression. Positive clones were selected by G418(1mg/ml) and GFP fusion protein was confirmed by immunoblotting analysis with anti-GFP antibodies. Interestingly, these cells demonstrated a higher percentage of mitotic abnormality including chromosome misalignment, anaphase bridging, lagging chromosome and multipolar spindles than controls after over 10 passages(20.0% vs 1.5%, p<0.01). To further clarify if this phenomenon resulted from chromosomal fusion, metaphase chromosome spreads were prepared. As expected, the TRF1 stable cells showed an elevated frequency of dicentric chromosomes compared with untransfected cells, which implicated chromosomal end-to-end fusion in these cells. Our results suggested high expression of TRF1 would induce chromosome missegregation at mitosis, a feature of chromosomal instability which is proposed to be a critical step in carcinogenesis. These findings bring fourth a new hint for our further understanding of carcinogenesis led by telomere dysfunction.

scholarly journals In silico pathway analysis based on Chromosomal Instability in Breast Cancer Patients

2020 ◽  
Author(s):  
AKEEN KOUR ◽  
Vasudha Sambyal ◽  
Kamlesh Guleria ◽  
Neeti Rajan Singh ◽  
Manjit Singh Uppal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Rna Polymerase Ii ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Pathway Analysis ◽  
Chromosomal Instability ◽  
Chromosome 1 ◽  
Breast Cancer Patients ◽  
Genomic Changes

Abstract Background: Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. Results: Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 hours Peripheral lymphocyte culturing and GTG-banding. Karyotypic analyses found more frequent chromosomal aberrations (structural and numerical) on chromosome 1, 2, 3, 4, 5, 8, 9, 17 and X. The data of genes harbored by chromosomal regions showing increased aberration frequency was retrieved from online databases. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. Conclusion: The chromosomal instability analysis in a non-target in cancer patients thus can be used to identify genes and decipher the pathway involved in tumorigenesis. The bioinformatics approach can help in identifying aberrant genes in transcription pathways and their relation with breast cancer progression.

scholarly journals In silico pathway analysis based on Chromosomal Instability in Breast Cancer Patients

2020 ◽  
Author(s):  
AKEEN KOUR ◽  
Vasudha Sambyal ◽  
Kamlesh Guleria ◽  
Neeti Rajan Singh ◽  
Manjit Singh Uppal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Rna Polymerase Ii ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Pathway Analysis ◽  
Chromosomal Instability ◽  
Chromosome 1 ◽  
Breast Cancer Patients ◽  
Genomic Changes

Abstract Background: Complex genomic changes that arise in tumors are a consequence of chromosomal instability. In tumor cells genomic aberrations disrupt core signaling pathways involving various genes, thus delineating of signaling pathways can help understand the pathogenesis of cancer. The bioinformatics tools can further help in identifying networks of interactions between the genes to get a greater biological context of all genes affected by chromosomal instability. Results: Karyotypic analyses was done in 150 clinically confirmed breast cancer patients and 150 age and gender matched healthy controls after 72 hours Peripheral lymphocyte culturing and GTG-banding. Karyotypic analyses found more frequent chromosomal aberrations (structural and numerical) on chromosome 1, 2, 3, 4, 5, 8, 9, 17 and X. The data of genes harbored by chromosomal regions showing increased aberration frequency was retrieved from online databases. Pathway analysis on a set of genes that were not linked together revealed that genes HDAC3, NCOA1, NLRC4, COL1A1, RARA, WWTR1, and BRCA1 were enriched in the RNA Polymerase II Transcription pathway which is involved in recruitment, initiation, elongation and dissociation during transcription. Conclusion: The chromosomal instability analysis in a non-target in cancer patients thus can be used to identify genes and decipher the pathway involved in tumorigenesis. The bioinformatics approach can help in identifying aberrant genes in transcription pathways and their relation with breast cancer progression.

Overexpression of microRNA-21 in the Serum of Breast Cancer Patients

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 58-63
Author(s):  
Batool Savari ◽  
Sohrab Boozarpour ◽  
Maryam Tahmasebi-Birgani ◽  
Hossein Sabouri ◽  
Seyed Mohammad Hosseini
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Tumor Resection ◽  
Tumor Grade ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Post Surgery ◽  
Polymerase Chain

Background: Breast cancer is the most common cancer diagnosed in women worldwide. So it seems that there's a good chance of recovery if it's detected in its early stages even before the appearances of symptoms. Recent studies have shown that miRNAs play an important role during cancer progression. These transcripts can be tracked in liquid samples to reveal if cancer exists, for earlier treatment. MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis, and breast tumor is no exception. Objective: The present study was aimed to track the miR-21 expression level in serum of the breast cancer patients in comparison with that of normal counterparts. Methods: Comparative real-time polymerase chain reaction was applied to determine the levels of expression of miR-21 in the serum samples of 57 participants from which, 42 were the patients with breast cancer including pre-surgery patients (n = 30) and post-surgery patients (n = 12), and the others were the healthy controls (n = 15). Results: MiR-21 was significantly over expressed in the serum of breast cancer patients as compared with healthy controls (P = 0.002). A significant decrease was also observed following tumor resection (P < 0.0001). Moreover, it was found that miR-21 overexpression level was significantly associated with tumor grade (P = 0.004). Conclusion: These findings suggest that miR-21 has the potential to be used as a novel breast cancer biomarker for early detection and prognosis, although further experiments are needed.

scholarly journals Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 268
Author(s):  
Marta Ferrari ◽  
Stefano Stagi
Keyword(s):  
Down Syndrome ◽  
Autoimmune Diseases ◽  
Normal Population ◽  
Underlying Mechanism ◽  
Short Review ◽  
Immune Dysregulation ◽  
Infectious Complications ◽  
Genetic Syndromes ◽  
Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

scholarly journals Immunometabolic Status of COVID-19 Cancer Patients

2020 ◽  
Vol 100 (4) ◽  
pp. 1839-1850
Author(s):  
A. Sica ◽  
M. P. Colombo ◽  
A. Trama ◽  
L. Horn ◽  
M. C. Garassino ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Macrophage Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Case Series ◽  
The United States ◽  
Alternative Activation ◽  
Nad Metabolism ◽  
Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

scholarly journals Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiao Wu ◽  
Sai-Ching Jim Yeung ◽  
Sicheng Liu ◽  
Aiham Qdaisat ◽  
Dewei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Cancer Patient ◽  
Nutrition Support ◽  
Immunodeficient Mice ◽  
The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

scholarly journals Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome

2018 ◽  
Vol 19 (11) ◽  
pp. 3675 ◽  
Author(s):  
Francesca Luisa Sciacca ◽  
Ambra Rizzo ◽  
Gloria Bedini ◽  
Fioravante Capone ◽  
Vincenzo Di Lazzaro ◽  
...  
Keyword(s):  
Internal Carotid ◽  
Neurofibromatosis Type ◽  
Genetic Syndromes ◽  
Genetic Syndrome ◽  
Susceptibility Factors ◽  
The Relationship ◽  
Genic Mutation ◽  
Internal Carotid Arteries ◽  
Cerebral Angiopathy

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal “moyamoya” vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.

scholarly journals Prediction of cancer progression in a group of 73 gastric cancer patients by circulating cell-free DNA

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Wang-Yang Pu ◽  
Rong Zhang ◽  
Li Xiao ◽  
Yong-You Wu ◽  
Wei Gong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Cell Free Dna ◽  
Free Dna ◽  
Gastric Cancer Patients ◽  
Circulating Cell Free Dna

scholarly journals Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1213
Author(s):  
Anca Irina Ristescu ◽  
Crina Elena Tiron ◽  
Adrian Tiron ◽  
Ioana Grigoras
Keyword(s):  
Cancer Patients ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Experimental Studies ◽  
Perioperative Period ◽  
Postoperative Recovery ◽  
Mesenchymal Transition ◽  
Oncological Treatment

Increased inspiratory oxygen concentration is constantly used during the perioperative period of cancer patients to prevent the potential development of hypoxemia and to provide an adequate oxygen transport to the organs, tissues and cells. Although the primary tumours are surgically removed, the effects of perioperative hyperoxia exposure on distal micro-metastases and on circulating cancer cells can potentially play a role in cancer progression or recurrence. In clinical trials, hyperoxia seems to increase the rate of postoperative complications and, by delaying postoperative recovery, it can alter the return to intended oncological treatment. The effects of supplemental oxygen on the long-term mortality of surgical cancer patients offer, at this point, conflicting results. In experimental studies, hyperoxia effects on cancer biology were explored following multiple pathways. In cancer cell cultures and animal models, hyperoxia increases the production of reactive oxygen species (ROS) and increases the oxidative stress. These can be followed by the induction of the expression of Brain-derived neurotrophic factor (BDNF) and other molecules involved in angiogenesis and by the promotion of various degrees of epithelial mesenchymal transition (EMT).

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