scholarly journals Clock genes and cancer development in particular in endocrine tissues

2019 ◽  
Vol 26 (6) ◽  
pp. R305-R317 ◽  
Author(s):  
Anna Angelousi ◽  
Eva Kassi ◽  
Narjes Ansari-Nasiri ◽  
Harpal Randeva ◽  
Gregory Kaltsas ◽  
...  
Keyword(s):  
Gene Disruption ◽  
Clock Gene ◽  
Clock Genes ◽  
Cancer Susceptibility ◽  
Chemotherapeutic Agents ◽  
Dna Damage And Repair ◽  
Normal Tissues ◽  
Oncogenic Pathways ◽  
Parathyroid Adenomas ◽  
Repair Mechanisms

Circadian rhythms at a central and peripheral level are operated by transcriptional/translational feedback loops involving a set of genes called ‘clock genes’ that have been implicated in the development of several diseases, including malignancies. Dysregulation of the Clock system can influence cancer susceptibility by regulating DNA damage and repair mechanisms, as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes’ epigenetic alterations, including hypermethylation of clock genes’ promoters or variants of clock genes. Clock gene disruption has been studied in breast, lung and prostate cancer, and haematological malignancies. However, it is still not entirely clear whether clock gene disruption is the cause or the consequence of tumourigenesis and data in endocrine neoplasms are scarce. Recent findings suggest that clock genes are implicated in benign and malignant adrenocortical neoplasias. They have been also associated with follicular and papillary thyroid carcinomas and parathyroid adenomas, as well as pituitary adenomas and craniopharyngiomas. Dysregulation of clock genes is also encountered in ovarian and testicular tumours and may also be related with their susceptibility to chemotherapeutic agents. The most common clock genes that are implicated in endocrine neoplasms are PER1, CRY1; in most cases their expression is downregulated in tumoural compared to normal tissues. Although there is still a lot to be done for the better understanding of the role of clock genes in endocrine tumourigenenesis, existing evidence could guide research and help identify novel therapeutic targets aiming mainly at the peripheral components of the clock gene system.

Cytoprotective Agents to Avoid Chemotherapy Induced Sideeffects on Normal Cells: A Review

2019 ◽  
Vol 19 (10) ◽  
pp. 765-781
Author(s):  
Seema Rohilla ◽  
Harish Dureja ◽  
Vinay Chawla
Keyword(s):  
Adverse Effects ◽  
Anticancer Agents ◽  
Therapeutic Index ◽  
Chemotherapeutic Agents ◽  
Vital Role ◽  
Normal Cells ◽  
Normal Tissues ◽  
Organ Specific ◽  
Delay In Treatment

Anticancer agents play a vital role in the cure of patients suffering from malignancy. Though, the chemotherapeutic agents are associated with various adverse effects which produce significant toxic symptoms in the patients. But this therapy affects both the malignant and normal cells and leads to constricted therapeutic index of antimalignant drugs which adversely impacts the quality of patients’ life. Due to these adversities, sufficient dose of drug is not delivered to patients leading to delay in treatment or improper treatment. Chemoprotective agents have been developed either to minimize or to mitigate the toxicity allied with chemotherapeutic agents. Without any concession in the therapeutic efficacy of anticancer drugs, they provide organ specific guard to normal tissues.

Synthesis and characterization of a new series of thiadiazole derivatives as potential anticancer agents

2020 ◽  
Vol 26 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
Serkan Levent ◽  
Begüm Nurpelin Sağlik ◽  
Betül Kaya Çavuşoğlu ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Anticancer Activities ◽  
Normal Tissues ◽  
H Nmr ◽  
Wide Range ◽  
Thiadiazole Derivatives ◽  
Low Efficiency

AbstractCancer is one of the most common causes of death in the world. Despite the importance of combating cancer in healthcare systems and research centers, toxicity in normal tissues and the low efficiency of anticancer drugs are major problems in chemotherapy. Nowadays the aim of many medical research projects is to discover new safer and more effective anticancer agents. 1,3,4-Thiadiazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities, including anticancer activities. The aim of this study was to determine the capacity of newly synthesized 1,3,4-thiadiazole compounds as chemotherapeutic agents. The structures of the obtained compounds were elucidated using 1H-NMR, 13C-NMR and mass spectrometry. Although the thiadiazole derivatives did not prove to be significantly cytotoxic to the tumour tissue cultures, compound 4i showed activity against the C6 rat brain cancer cell line (IC50 0.097 mM) at the tested concentrations.

scholarly journals DNA Repair: Exploiting the Fanconi Anemia Pathway As a Potential Therapeutic Target

2011 ◽  
pp. 453-465 ◽  
Author(s):  
T. HUCL ◽  
E. GALLMEIER
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Susceptibility ◽  
Synthetic Lethality ◽  
Bone Marrow Failure ◽  
Long Term Effects ◽  
Alternative Pathways ◽  
Repair Mechanisms ◽  
Relationship Of

DNA repair is an active cellular process to respond to constant DNA damage caused by metabolic processes and environmental factors. Since the outcome of DNA damage is generally adverse and long term effects may contribute to oncogenesis, cells have developed a variety of DNA repair mechanisms, which operate depending on the type of DNA damage inflicted. At least 15 Fanconi anemia (FA) proteins interact in a common pathway involved in homologous recombination. Inherited homozygous mutations in any of these FA genes cause a rare disease, Fanconi anemia, characterized by congenital abnormalities, progressive bone-marrow failure and cancer susceptibility. Heterozygous germline FA mutations predispose to various types of cancer. In addition, somatic FA mutations have been identified in diverse cancer types. Evidence exists that cells deficient in the FA pathway become dependent on alternative pathways for survival. Additional inhibition of such alternative pathways is thus expected to result in cell death, creating a relationship of synthetic lethality. Identifying these relationships can reveal yet unknown mechanisms of DNA repair and new targets for therapy.

scholarly journals Landscape Of HOXA Genes Methylation in Colorectal Cancer

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Muhiddin Ishak ◽  
Rashidah Baharudin ◽  
Loh Teng-Hern Tan ◽  
Learn-Han Lee ◽  
Nurul-Syakima Ab Mutalib
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Cpg Islands ◽  
Methylation Pattern ◽  
Gene Promoters ◽  
Normal Tissues ◽  
Genes Encoding ◽  
Hoxa Genes ◽  
A Minor ◽  
Hoxa Gene

Colorectal cancer (CRC) is among the most common cancers worldwide and the second leading cause of cancer-related death in Malaysia. The HOXA gene cluster is a family of Homeobox A genes encoding transcriptional regulators that play vital roles in cancer susceptibility and progression. Dysregulated HOXA expression influences various aspects of carcinogenesis processes. Therefore, this study aims to elucidate the methylation landscape of HOXA genes in CRC. Twelve pairs of CRC — adjacent normal tissues were subjected to Infinium DNA MethyEPIC array. Differentially methylatedregions were identified using the ChAMP Bioconductor and methylation levels of HOXA genes were manually curated. We identified 100 significantly differentially methylated probes annotated to HOXA genes. HOXA3 has the highest number of differentially methylated probes (n=27), followed by HOXA2 (n=20) and HOXA4 (n=14). The majority (43%) of the probes were located at the transcription start site (TSS) 200, which is one of the gene promoters. In respect to CpG islands (CGI), the probes were equally located in the island and shore regions (47% each) while a minor percentage was in the shelf (6%). Our work gave a comprehensive assessment of the DNA methylation pattern of HOXA genes and provide the first evidence of HOXA2, HOXA3 and HOXA4 differential methylation in Malaysian CRC. The new knowledge from this study can be utilized to further increase our understanding of CRC methylomics, particularly on the homeobox A genes. The prognostic and diagnostic roles of the differentially methylated HOXA genes warrant future investigations.

scholarly journals Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Victor D. Martinez ◽  
Emily A. Vucic ◽  
Marta Adonis ◽  
Lionel Gil ◽  
Wan L. Lam
Keyword(s):  
Dna Damage ◽  
Drinking Water ◽  
Repair Process ◽  
Dna Methyltransferases ◽  
Health Concern ◽  
Dna Damage And Repair ◽  
Repair Mechanisms ◽  
Contaminated Drinking Water ◽  
High Concentrations ◽  
Epigenetic Patterns

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

Melatonergic index as a prognostic biomarker of reproductive organ cancers: correlations with metabolic parameters as well as clock genes PER1 and TIMELESS

2021 ◽  
Vol 4 (2) ◽  
pp. 299-315
Author(s):  
Luiz Gustavo De Almeida Chuffa ◽  
Robson F Carvalho ◽  
Fábio R Seiva ◽  
Debora Aparecida Pires de Campos Zuccari ◽  
Russel J Reiter
Keyword(s):  
Survival Rate ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Profiles ◽  
Tumor Staging ◽  
Reproductive Organ ◽  
Cancer Diagnostics ◽  
The Cancer Genome Atlas ◽  
Metabolic Enzyme ◽  
Endometrial Cancers

Cancers of the reproductive organs are often hard to be detected, and patients’ survival rate drops considerably even when the tumor is removed. Based on the fact that melatonin levels are significantly lower in cancer cells than that in the healthy cells, and this melatonin suppression remains during tumor progression, we have examined a simple two-gene-based melatonergic system [the indices of melatonin synthesis and metabolism (ASMT:CYP1A1, ASMT:CYP1A2, ASMT:CYP1B1)] as a prognostic factor for reproductive organ cancer survival rate. RNA-seq data from The Cancer Genome Atlas (TCGA) of seven types of human reproductive organ tumors (n = 3571 samples) were analyzed. By stratifying the set of index values into high vs low risk, we observed that patients with a high melatonergic index had improved survival rates for cervical, ovarian, and endometrial cancers. Patients at high-risk (low melatonergic index) showed a trend of diagnosis of breast, prostate, and testicular cancers at the younger age, while patients with cervical, ovarian, and endometrial cancers presented with higher tumor staging. The melatonergic indices, especially the ASMT:CYP1B1, positively correlated with the clock gene PER1 while negatively correlated with the clock gene TIMELESS in all reproductive organ cancers. We further analyzed the correlation between the expression profiles of the melatonin-synthesizing enzyme (ASMT gene) with metabolic enzyme-encoding genes. Notably, LDHA, PDK1, and PDHA1 showed a higher correlation in male and female reproductive organ tumors, while IDH1, SDHB, GLS, and ATP1A1 had a positive correlation in breast, testicular, and endometrial cancers. These results have provided a comprehensive evaluation of the melatonergic system in relation to the reproductive organ tumor microenvironment and identified promising gene signatures as potential biomarkers for cancer diagnostics, prognostics, and therapeutics.

Integrated Microarray-based Tools for Detection of Genomic DNA Damage and Repair Mechanisms

2017 ◽  
pp. 77-99 ◽  
Author(s):  
Patrick van Eijk ◽  
Yumin Teng ◽  
Mark R. Bennet ◽  
Katie E. Evans ◽  
James R. Powell ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genomic Dna ◽  
Dna Damage And Repair ◽  
Repair Mechanisms

PREMONition: An algorithm for predicting the circadian clock-regulated molecular network

2018 ◽  
Author(s):  
Jasper Bosman ◽  
Zheng Eelderink-Chen ◽  
Emma Laing ◽  
Martha Merrow
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Circadian Clocks ◽  
Model Systems ◽  
Functional Relationships ◽  
Growth Assay ◽  
Living Organisms ◽  
Clock Mechanism ◽  
Transcriptional Feedback

AbstractA transcriptional feedback loop is central to clock function in animals, plants and fungi. The clock genes involved in its regulation are specific to - and highly conserved within - the kingdoms of life. However, other shared clock mechanisms, such as phosphorylation, are mediated by proteins found broadly among living organisms, performing functions in many cellular sub-systems. Use of homology to directly infer involvement/association with the clock mechanism in new, developing model systems, is therefore of limited use. Here we describe the approach PREMONition,PREdictingMolecularNetworks, that uses functional relationships to predict molecular circadian clock associations. PREMONition is based on the incorporation of proteins encoded by known clock genes (when available), rhythmically expressed clock-controlled genes and non-rhythmically expressed but interacting genes into a cohesive network. After tuning PREMONition on the networks derived for human, fly and fungal circadian clocks, we deployed the approach to predict a molecular clock network forSaccharomyces cerevisiae, for which there are no readily-identifiable clock gene homologs. The predicted network was validated using gene expression data and a growth assay for sensitivity to light, a zeitgeber of circadian clocks of most organisms. PREMONition may be used to identify candidate clock-regulated processes and thus candidate clock genes in other organisms.

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