RNAi treatment has been shown to successfully modify human-related target gene expression, including cancer. It has the capacity to control non-standard oncogenes, such as oncogenic lncRNAs

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Cancer Cells ◽  
Target Genes ◽  
Environmental Changes ◽  
Sirna Delivery ◽  
Cost Effective ◽  
Clinical Development ◽  
Related Target ◽  
Chemical Structures ◽  
Rnai Therapeutics ◽  
Lipid Structures

Recent breakthroughs in clinical research and deployment of RNAi therapeutics have validated siRNA's promise to cure human diseases. RNAi therapy has been proven to effectively alter the expression of human-related target genes, including cancer. It has the potential to regulate oncogenes not addressed by standard treatment, such as oncogenic lncRNAs, to treat cancer more successfully. Due to their intrinsic liver affinity, successful RNAi therapies in clinical development primarily target liver diseases. Systemic dispersion of therapeutic siRNAs is an effective cancer therapy technique, especially for advanced diseases. Despite recent advances in siRNA delivery technologies, a problem remains with efficiently distributing siRNAs into solid tumors and cancer cells. To overcome several challenges to the dispersion of siRNA in cancer cells' cytoplasm, novel and highly effective delivery systems need to be devised. Delivery devices' ability to sense and adjust to environmental changes throughout the delivery process can make cytosolic distribution into cancer cells more efficient and accurate. Due to their well-defined and simple chemical structures and their multifunctionalities to respond to environmental changes to facilitate efficient cytosolic transport, environment-responsive lipids are promising platforms for clinical development to deliver siRNA. The primary benefit of simple, well-defined lipid structures over complex systems for cost-effective CMC and clinical translation is the simple, well-defined lipid structures. Environment-responsive lipids might be considered as simple, clever siRNA delivery methods that can overcome delivery difficulties for successful cancer treatment.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli
Keyword(s):  
Drug Targets ◽  
Redox Homeostasis ◽  
Cost Effective ◽  
Structural Features ◽  
Mammalian Host ◽  
Neglected Diseases ◽  
Nitrogen Compounds ◽  
Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

Azo (Hydrazone) pigments: general principles

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Robert Christie
Keyword(s):  
High Performance ◽  
Metal Salt ◽  
Low Cost ◽  
Cost Effective ◽  
Precipitation Process ◽  
Ambient Temperatures ◽  
Technical Performance ◽  
Chemical Structures ◽  
General Chemical ◽  
Physical Form

Abstract This paper presents an overview of the general chemical principles underlying the structures, synthesis and technical performance of azo pigments, the dominant chemical class of industrial organic pigments in the yellow, orange, and red shade areas, both numerically and in terms of tonnage manufactured. A description of the most significant historical features in this group of pigments is provided, starting from the discovery of the chemistry on which azo colorants are based by Griess in the mid-nineteenth century, through the commercial introduction of the most important classical azo pigments in the early twentieth century, including products known as the Hansa Yellows, β-naphthol reds, including metal salt pigments, and the diarylide yellows and oranges, to the development in the 1950s and 1960s of two classes of azo pigments that exhibit high performance, disazo condensation pigments and benzimidazolone-based azo pigments. A feature that complicates the description of the chemical structures of azo pigments is that they exist in the solid state as the ketohydrazone rather than the hydroxyazo form, in which they have been traditionally been illustrated. Numerous structural studies conducted over the years on an extensive range of azo pigments have demonstrated this feature. In this text, they are referred to throughout as azo (hydrazone) pigments. Since a common synthetic procedure is used in the manufacture of virtually all azo (hydrazone) pigments, this is discussed in some detail, including practical aspects. The procedure brings together two organic components as the fundamental starting materials, a diazo component and a coupling component. An important reason for the dominance of azo (hydrazone) pigments is that they are highly cost-effective. The syntheses generally involve low cost, commodity organic starting materials and are carried out in water as the reaction solvent, which offers obvious economic and environmental advantages. The versatility of the approach means that an immense number of products may be prepared, so that they have been adapted structurally to meet the requirements of many applications. On an industrial scale, the processes are straightforward, making use of simple, multi-purpose chemical plant. Azo pigments may be produced in virtually quantitative yields and the processes are carried out at or below ambient temperatures, thus presenting low energy requirements. Finally, provided that careful control of the reaction conditions is maintained, azo pigments may be prepared directly by an aqueous precipitation process that can optimise physical form, with control of particle size distribution, crystalline structure, and surface character. The applications of azo pigments are outlined, with more detail reserved for subsequent papers on individual products.

Androgen receptor: acting in the three-dimensional chromatin landscape of prostate cancer cells

2011 ◽  
Vol 5 (1) ◽  
Author(s):  
Harri Makkonen ◽  
Jorma J. Palvimo
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Binding Sites ◽  
Target Genes ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Gene Promoters ◽  
Loop Formation ◽  
Prostate Cancer Cells

AbstractAndrogen receptor (AR) acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the level of genes and gene programs. Defective AR signaling leads to a wide array of androgen insensitivity disorders, and deregulated AR function, in particular overexpression of AR, is involved in the growth and progression of prostate cancer. Classic models of AR action view AR-binding sites as upstream regulatory elements in gene promoters or their proximity. However, recent wider genomic screens indicate that AR target genes are commonly activated through very distal chromatin-binding sites. This highlights the importance of long-range chromatin regulation of transcription by the AR, shifting the focus from the linear gene models to three-dimensional models of AR target genes and gene programs. The capability of AR to regulate promoters from long distances in the chromatin is particularly important when evaluating the role of AR in the regulation of genes in malignant prostate cells that frequently show striking genomic aberrations, especially gene fusions. Therefore, in addition to the mechanisms of DNA loop formation between the enhancer bound ARs and the transcription apparatus at the target core promoter, the mechanisms insulating distally bound ARs from promiscuously making contacts and activating other than their normal target gene promoters are critical for proper physiological regulation and thus currently under intense investigation. This review discusses the current knowledge about the AR action in the context of gene aberrations and the three-dimensional chromatin landscape of prostate cancer cells.

scholarly journals Recruitment of NCOR1 to VDR target genes is enhanced in prostate cancer cells and associates with altered DNA methylation patterns

2012 ◽  
Vol 34 (2) ◽  
pp. 248-256 ◽  
Author(s):  
C. L. Doig ◽  
P. K. Singh ◽  
V. K. Dhiman ◽  
J. L. Thorne ◽  
S. Battaglia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Target Genes ◽  
Prostate Cancer Cells ◽  
Methylation Patterns

scholarly journals In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 394 ◽  
Author(s):  
Viktor Maurer ◽  
Selin Altin ◽  
Didem Ag Seleci ◽  
Ajmal Zarinwall ◽  
Bilal Temel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Superparamagnetic Iron Oxide ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Therapy Outcome ◽  
Ionic Surfactant ◽  
Combinational Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

scholarly journals Synthesizing artificial devices that redirect cellular information at will

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yuchen Liu ◽  
Jianfa Li ◽  
Zhicong Chen ◽  
Weiren Huang ◽  
Zhiming Cai
Keyword(s):  
Cancer Cells ◽  
Signaling Pathway ◽  
Gene Networks ◽  
Target Genes ◽  
Logic Gates ◽  
Feedback Loops ◽  
Oncogenic Signaling ◽  
Multiple Signals ◽  
Translational Level ◽  
At Will

Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectors—a series of RNA devices—that connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways. Furthermore, logical AND gates based on these devices and integration of multiple signals have been used successfully for identification and redirection of the state of cancer cells. Eventually, the malignant phenotypes of cancers have been reversed by rewiring the oncogenic signaling from promoting to suppressing tumorigenesis. We provide a novel platform for redirecting cellular information.

scholarly journals Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Pricila da Silva Cunha ◽  
Heloisa B. Pena ◽  
Carla Sustek D’Angelo ◽  
Celia P. Koiffmann ◽  
Jill A. Rosenfeld ◽  
...  
Keyword(s):  
Real Time ◽  
Diagnostic Test ◽  
Quantitative Pcr ◽  
Target Genes ◽  
Cost Effective ◽  
Qpcr Assay ◽  
Deletion Syndrome ◽  
Comparative Genomic ◽  
Real Time Quantitative Pcr ◽  
Subtelomeric Deletion

Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36:PRKCZandSKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescentin situhybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR ofPRKCZandSKIis a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs.

scholarly journals Adaptive sensing scheme using naive Bayes classification for environment monitoring with drone

2018 ◽  
Vol 14 (1) ◽  
pp. 155014771875603 ◽  
Author(s):  
Yao-Hua Ho ◽  
Yu-Te Huang ◽  
Hao-Hua Chu ◽  
Ling-Jyh Chen
Keyword(s):  
Environmental Changes ◽  
Naive Bayes ◽  
Cost Effective ◽  
Parameter Tuning ◽  
Naïve Bayes ◽  
Spatial Distance ◽  
Environmental Sensors ◽  
Adaptive Sensing ◽  
Naive Bayes Classification ◽  
Naïve Bayes Classification

Environmental sensors are important for collecting data to understand environmental changes and analyze environmental issues. In order to effectively monitor environmental changes, high-density sensor deployment and evenly distributed spatial distance between sensors become the requirements and desired properties for such applications. In many applications, sensors are deployed in locations that are difficult and dangerous to reach (e.g. mountaintop or skyscraper roof). To collect data from those sensors, unmanned aerial vehicles are used to act as data mules to overcome the problem of collecting data in challenging environments. In this article, we extend the adaptive return-to-home sensing algorithm with a parameter-tuning algorithm that combines naive Bayes classification and binary search to adapt adaptive return-to-home sensing parameters effectively on the fly. The proposed approach is able to (1) optimize number of sensing attempts, (2) reduce oscillation of the distance for consecutive attempts, and (3) reserve enough power for drone to return-to-home. Our results show that the naive Bayes classification–enhanced adaptive return-to-home sensing scheme is able to avoid oscillation in sensing and guarantees return-to-home feature while behaving more cost-effective in parameter tuning than the other machine learning–based approaches.

scholarly journals Comparative analysis of sigma factors RpoS, FliA, and RpoN in Edwardsiella tarda

2016 ◽  
Vol 62 (10) ◽  
pp. 861-869 ◽  
Author(s):  
ShanShan Song ◽  
Yuanyuan Xue ◽  
Enfu Liu ◽  
Keping Wang ◽  
Yuanxing Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Genes ◽  
Environmental Changes ◽  
Growth Stress ◽  
Sigma Factors ◽  
Edwardsiella Tarda ◽  
Proteomics Analysis ◽  
Ionization Time ◽  
Reverse Transcription Pcr ◽  
Flight Mass Spectrometry

Sigma factors are important regulators that bacteria employ to cope with environmental changes. Studies on the functions of sigma factors have uncovered their roles in many important cellular activities, such as growth, stress tolerance, motility, biofilm formation, and virulence. However, comparative analyses of sigma factors that examine their common and unique features or elucidate their cross-regulatory relationships have rarely been conducted for Edwardsiella tarda. Here, we characterized and compared motility and resistance to oxidative stress of E. tarda strains complemented with rpoS, fliA, and rpoN mutants. The results suggest that the sigma factors FliA and RpoN regulated motility, whereas RpoS exhibited no such function. RpoS and RpoN were essential for oxidative stress resistance, whereas FliA had no obvious impact under oxidative stress conditions. Furthermore, 2-dimensional gel electrophoresis based proteomics analysis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry revealed 12 differentially expressed protein spots that represented 11 proteins between the mutant and wild-type strains. Quantification of the expression of target genes by quantitative reverse transcription PCR confirmed the results of our proteomics analysis. Collectively, these results suggest that these sigma factors are multifunctional mediators involved in controlling the expression of many metabolic pathway genes.

scholarly journals Identification of target genes in breast cancer cells directly regulated by the SRC-3/AIB1 coactivator

2005 ◽  
Vol 102 (5) ◽  
pp. 1339-1344 ◽  
Author(s):  
P. Labhart ◽  
S. Karmakar ◽  
E. M. Salicru ◽  
B. S. Egan ◽  
V. Alexiadis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes
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