scholarly journals Comprehensive analysis of mutational signatures in pediatric cancers

2021 ◽  
Author(s):  
Venu Thatikonda ◽  
S.M Ashiqul Islam ◽  
Barbara C. Jones ◽  
Susanne N. Groebner ◽  
Gregor Warsow ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Tumor Biology ◽  
Future Research ◽  
Mutational Signatures ◽  
Mutation Status ◽  
Cancer Subtypes ◽  
Pediatric Cancers ◽  
Significant Difference ◽  
Recombination Repair ◽  
Repair Defect

Analysis of mutational signatures can reveal the underlying molecular mechanisms of the processes that have imprinted the somatic mutations found in a cancer genome. Here, we present a pan-cancer mutational signatures analysis of single base substitutions (SBS) and small insertion and deletions (ID) in pediatric cancers encompassing 537 whole genome sequenced tumors from 20 molecularly defined cancer subtypes. We identified only a small number of mutational signatures active in pediatric cancers when compared to the previously analyzed adult cancers. Further, we report a significant difference in the proportion of pediatric tumors which show homologous recombination repair defect signature SBS3 compared to prior analyses. Correlating genomic alterations with signature activities, we identified an association of TP53 mutation status with substitution signatures SBS2, SBS8, SBS13 and indel signatures ID2 and ID9, as well as chromothripsis associated with SBS8, SBS40 and ID9. This analysis provides a systematic overview of COSMIC v.3 SBS and ID mutational signatures active across pediatric cancers, which is highly relevant for understanding tumor biology as well as enabling future research in defining biomarkers of treatment response.

scholarly journals Identification of key genes and associated pathways in neuroendocrine tumors through bioinformatics analysis and predictions of small drug molecules

2020 ◽  
Author(s):  
Praveenkumar Devarbhavi ◽  
Basavaraj Vastrad ◽  
Anandkumar Tengli ◽  
Chanabasayya Vastrad ◽  
Iranna Kotturshetti
Keyword(s):  
Drug Target ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Regulatory Elements ◽  
Future Research ◽  
High Morbidity ◽  
Hub Genes ◽  
Go Enrichment ◽  
Significant Difference

AbstractNeuroendocrine tumor (NET) is one of malignant cancer and is identified with high morbidity and mortality rates around the world. With indigent clinical outcomes, potential biomarkers for diagnosis, prognosis and drug target are crucial to explore. The aim of this study is to examine the gene expression module of NET and to identify potential diagnostic and prognostic biomarkers as well as to find out new drug target. The differentially expressed genes (DEGs) identified from GSE65286 dataset was used for pathway enrichment analyses and gene ontology (GO) enrichment analyses and protein - protein interaction (PPI) analysis and module analysis. Moreover, miRNAs and transcription factors (TFs) that regulated the up and down regulated genes were predicted. Furthermore, validation of hub genes was performed. Finally, molecular docking studies were performed. DEGs were identified, including 453 down regulated and 459 up regulated genes. Pathway and GO enrichment analysis revealed that DEGs were enriched in sucrose degradation, creatine biosynthesis, anion transport and modulation of chemical synaptic transmission. Important hub genes and target genes were identified through PPI network, modules, target gene - miRNA network and target gene - TF network. Finally, survival analyses, receiver operating characteristic (ROC) curve and RT-PCR validated the significant difference of ATP1A1, LGALS3, LDHA, SYK, VDR, OBSL1, KRT40, WWOX, NINL and PPP2R2B between metastatic NET and normal controls. In conclusion, the DEGs and hub genes with their regulatory elements identified in this study will help us understand the molecular mechanisms underlying NET and provide candidate targets for future research.

Molecular Mechanisms Underlying the Functions of Cellular Markers Associated with the Phenotype of Cancer Stem Cells

2019 ◽  
Vol 14 (5) ◽  
pp. 405-420 ◽  
Author(s):  
Eduardo Alvarado-Ortiz ◽  
Miguel Á. Sarabia-Sánchez ◽  
Alejandro García-Carrancá
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Molecular Mechanisms ◽  
Tumor Biology ◽  
Molecular Tools ◽  
Recent Past ◽  
Functional Roles ◽  
Cellular Population ◽  
Cellular Markers ◽  
A Minor

Cancer Stem Cells (CSC) generally constitute a minor cellular population within tumors that exhibits some capacities of normal Stem Cells (SC). The existence of CSC, able to self-renew and differentiate, influences central aspects of tumor biology, in part because they can continue tumor growth, give rise to metastasis, and acquire drug and radioresistance, which open new avenues for therapeutics. It is well known that SC constantly interacts with their niche, which includes mesenchymal cells, extracellular ligands, and the Extra Cellular Matrix (ECM). These interactions regularly lead to homeostasis and maintenance of SC characteristics. However, the exact participation of each of these components for CSC maintenance is not clear, as they appear to be context- or cell-specific. In the recent past, surface cellular markers have been fundamental molecular tools for identifying CSC and distinguishing them from other tumor cells. Importantly, some of these cellular markers have been shown to possess functional roles that affect central aspects of CSC. Likewise, some of these markers can participate in regulating the interaction of CSC with their niche, particularly the ECM. We focused this review on the molecular mechanisms of surface cellular markers commonly employed to identify CSC, highlighting the signaling pathways and mechanisms involved in CSC-ECM interactions, through each of the cellular markers commonly used in the study of CSC, such as CD44, CD133, CD49f, CD24, CXCR4, and LGR5. Their presence does not necessarily implicate them in CSC biology.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Current gene panels account for nearly all homologous recombination repair-associated multiple-case breast cancer families

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Thibaut S. Matis ◽  
Nadia Zayed ◽  
Bouchra Labraki ◽  
Manon de Ladurantaye ◽  
Théophane A. Matis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Large Fraction ◽  
Homologous Recombination Repair ◽  
Mutational Signatures ◽  
Recombination Repair ◽  
Multiple Case ◽  
Gene Panels ◽  
Tumor Dna

AbstractIt was hypothesized that variants in underexplored homologous recombination repair (HR) genes could explain unsolved multiple-case breast cancer (BC) families. We investigated HR deficiency (HRD)-associated mutational signatures and second hits in tumor DNA from familial BC cases. No candidates genes were associated with HRD in 38 probands previously tested negative with gene panels. We conclude it is unlikely that unknown HRD-associated genes explain a large fraction of unsolved familial BC.

scholarly journals The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

2021 ◽  
Vol 18 (9) ◽  
pp. 5038
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Maria Clara La Rosa ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pilot Study ◽  
Alcohol Consumption ◽  
Telomere Length ◽  
Molecular Mechanisms ◽  
Epidemiological Studies ◽  
Potential Association ◽  
Significant Difference ◽  
Periconceptional Period ◽  
Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

scholarly journals The Sex Determination Cascade in the Silkworm

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 315
Author(s):  
Xu Yang ◽  
Kai Chen ◽  
Yaohui Wang ◽  
Dehong Yang ◽  
Yongping Huang
Keyword(s):  
Sex Determination ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Model Species ◽  
Male And Female ◽  
Master Regulators ◽  
Primary Signal ◽  
Basic Understanding ◽  
Female Specific ◽  
Working Mechanisms

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.

scholarly journals Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3571
Author(s):  
Bonglee Kim ◽  
Ji-Eon Park ◽  
Eunji Im ◽  
Yongmin Cho ◽  
Jinjoo Lee ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Clinical Implications ◽  
Research Perspectives ◽  
Current Review ◽  
Gold Silver ◽  
Significant Efficacy ◽  
Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

The role of heredity in cancer.

1989 ◽  
Vol 7 (4) ◽  
pp. 527-540 ◽  
Author(s):  
E G Levine ◽  
R A King ◽  
C D Bloomfield
Keyword(s):  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Tumor Development ◽  
Future Research ◽  
Minor Role ◽  
Research Activity ◽  
Environmental Interactions ◽  
Future Research Directions ◽  
A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

scholarly journals Stock Market Reaction to COVID-19: Evidence in Customer Goods Sector with the Implication for Open Innovation

2020 ◽  
Vol 6 (4) ◽  
pp. 99
Author(s):  
Zaky Machmuddah ◽  
St. Dwiarso Utomo ◽  
Entot Suhartono ◽  
Shujahat Ali ◽  
Wajahat Ali Ghulam
Keyword(s):  
Stock Prices ◽  
Stock Price ◽  
Practical Implication ◽  
Efficient Market Hypothesis ◽  
Future Research ◽  
Observation Data ◽  
Economic Sectors ◽  
Significant Difference ◽  
Before And After ◽  
Long Term Impact

The coronavirus pandemic has spread all over the world, affecting both the health and economic sectors. The aim of this research was to observe stock prices of customer goods before and after the COVID-19 pandemic using event study and the comparison test. The sample included data of daily closing stock prices and volume of stock trade during the three months before (−90 days) and after (+90 days) the occurrence of the COVID-19 pandemic ongoing, totaling 2670 observation data both before and after the COVID-19 pandemic, for a total of 5340. The research findings indicate a significant difference between the daily closing stock price and volume of stock trade before and after the COVID-19 pandemic. The current research has both theoretical and practical implications: the findings strengthen the efficient market hypothesis, which states that the more complete the provided information, the more efficient the market. The practical implication is that investors should be careful when choosing to invest. Investors should choose customer goods sector companies that provide products that are much needed by customers, for example, pharmacy, food, beverages, etc. Future research is needed to investigate the long-term impact of the pandemic on the economy.

scholarly journals A microbiome engineering framework to evaluate rhizobial symbionts of legumes

2021 ◽  
Author(s):  
Kenjiro W. Quides ◽  
Hagop S. Atamian
Keyword(s):  
Molecular Mechanisms ◽  
Future Research ◽  
Agricultural Systems ◽  
Legume Crops ◽  
Rhizobial Inoculants

Abstract Background For well over a century, rhizobia have been recognized as effective biofertilizer options for legume crops. This has led to the widespread use of rhizobial inoculants in agricultural systems, but a recurring issue has emerged: applied rhizobia struggle to provide growth benefits to legume crops. This has largely been attributed to the presence of soil rhizobia and has been termed the ‘rhizobial competition problem.’ Scope Microbiome engineering has emerged as a methodology to circumvent the rhizobial competition problem by creating legume microbiomes that do not require exogenous rhizobia. However, we highlight an alternative implementation of microbiome engineering that focuses on untangling the complexities of the symbiosis that contribute to the rhizobial competition problem. We outline three approaches that use different starting inocula to test hypotheses to overcome the rhizobial competition problem. Conclusions The approaches we suggest are targeted at various stages of the legume-rhizobium symbiosis and will help us uncover underlying molecular mechanisms that contribute to the rhizobial competition problem. We conclude with an integrative perspective of these different approaches and suggest a path forward for future research on legumes and their complex microbiome.

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