scholarly journals Profiling Cancer Cells by Cell-SELEX: Use of Aptamers for Discovery of Actionable Biomarkers and Therapeutic Applications Thereof

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 28
Author(s):  
Sarah Shigdar ◽  
Lisa Agnello ◽  
Monica Fedele ◽  
Simona Camorani ◽  
Laura Cerchia
Keyword(s):  
High Complexity ◽  
Early Assessment ◽  
Clinical Biomarkers ◽  
Personalized Cancer Medicine ◽  
Specific Cancer ◽  
Cancer Types ◽  
Enrichment Technology ◽  
Systematic Evolution ◽  
Personalized Cancer ◽  
Exponential Enrichment

The identification of tumor cell-specific surface markers is a key step towards personalized cancer medicine, allowing early assessment and accurate diagnosis, and development of efficacious targeted therapies. Despite significant efforts, currently the spectrum of cell membrane targets associated with approved treatments is still limited, causing an inability to treat a large number of cancers. What mainly limits the number of ideal clinical biomarkers is the high complexity and heterogeneity of several human cancers and still-limited methods for molecular profiling of specific cancer types. Thanks to the simplicity, versatility and effectiveness of its application, cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology is a valid complement to the present strategies for biomarkers’ discovery. We and other researchers worldwide are attempting to apply cell-SELEX to the generation of oligonucleotide aptamers as tools for both identifying new cancer biomarkers and targeting them by innovative therapeutic strategies. In this review, we discuss the potential of cell-SELEX for increasing the currently limited repertoire of actionable cancer cell-surface biomarkers and focus on the use of the selected aptamers as components of innovative conjugates and nano-formulations for cancer therapy.

scholarly journals Novel Drug Screening Platform: Tumor Organoid

2021 ◽  
Vol 26 (4) ◽  
pp. 233-240
Author(s):  
Ju Eun Maeng ◽  
Ha-Young Seo ◽  
Soon-Chan Kim ◽  
Ja-Lok Ku
Keyword(s):  
Drug Screening ◽  
Tumor Tissue ◽  
Ductal Adenocarcinoma ◽  
Personalized Cancer Medicine ◽  
Cancer Types ◽  
Screening Platform ◽  
And Function ◽  
Personalized Cancer ◽  
Novel Drug ◽  
Fitting Model

Pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal cancers among all cancer types, with a relative 5-year survival rate of less than 8%. Currently, surgery is the only probable curative treatment for PDAC which is available for only 10-15% of the patients diagnosed with the cancer. Organoids resemble the original tissue in morphology and function with self-organizing capacity. Organoids can be cultured with high effectiveness from individual patient derived tumor tissue which makes them an extremely fitting model for translational uses and the improvement of personalized cancer medicine. Before personalized medicine based on organoids can be applied in the clinic, the improvement of drug screening platforms in terms of sensitivity and robustness is necessary.

Cancer in agricultural populations

2020 ◽  
pp. 837-837
Author(s):  
K. . Togawa
Keyword(s):  
Risk Factors ◽  
General Population ◽  
Cohort Studies ◽  
Health Effects ◽  
Cancer Incidence ◽  
Lower Prevalence ◽  
International Consortium ◽  
Adverse Health Effects ◽  
Specific Cancer ◽  
Cancer Types

Agricultural workers can be exposed to a wide variety of agents (e.g. pesticides), some of which may have adverse health effects, such as cancer. To study the health effects of agricultural exposures, an international consortium of agricultural cohort studies, AGRICOH, was established. The present analysis compared cancer incidence between the AGRICOH cohorts and the general population and found lower overall cancer incidence in the AGRICOH cohorts, with some variation across cohorts for specific cancer types. The observed lower cancer incidence may be due to healthy worker bias or lower prevalence of risk factors in the agricultural populations. Further analysis is underway.

FEATURES OF ORGANOPHOSPHATES IMMOBILIZATION VIA STREPTAVIDIN-BIOTIN SYSTEM FOR EXPERIMENTS ON SELECTION OF APTAMERS

2020 ◽  
pp. 12-20
Author(s):  
D. A. Belinskaya ◽  
Yu. V. Chelusnova ◽  
V. V. Abzianidze ◽  
N. V. Goncharov
Keyword(s):  
Polyethylene Glycol ◽  
Organophosphorus Compounds ◽  
Binding Energies ◽  
Rna Aptamers ◽  
Main Method ◽  
Modeling Methods ◽  
Molecular Dynamics Methods ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

Poisoning with organophosphorus compounds occupy one of the leading places in exotoxicosis. At the first stage, the detoxification of organophosphates can be provided with the help of DNA or RNA aptamers that bind the poison in the bloodstream. Currently, the main method of searching for aptamers is the experimental method of systematic evolution of ligands by exponential enrichment (SELEX). In the process of aptamer selection, the target molecule must be immobilized via the streptavidin-biotin complex. Since the poison molecule is small in size, to increase its availability for binding to aptamer, it is necessary to use a spacer between organophosphorus compounds and biotin. The aim of this work was to optimize the selection of aptamers for organophosphorus compounds by increasing the availability of a poison molecule immobilized via the streptavidin-biotin complex on the example of paraoxon. For this purpose, three spacers between organophosphorus compounds and biotin were tested using molecular modeling methods: three links of polyethylene glycol (3-PEG), four links of polyethylene glycol (4-PEG) and aminohexyl. The conformation of the biotinylated paraoxon complex with streptavidin and the interaction of paraoxon with the binding fragment of the aptamer were modeled using molecular docking and molecular dynamics methods. The ability of biotinylated paraoxon to bind to the aptamer has been evaluated by analyzing the surface area of the paraoxon available to the solvent, as well as by calculating the free binding energies. It has been shown that only in the case of aminohexyl immobilized paraoxon can contact the aptamer. At the final stage, the synthesis of paraoxon bound to biotin via aminohexyl was carried out.

scholarly journals Personalized Cancer Medicine in the Media: Sensationalism or Realistic Reporting?

2021 ◽  
Vol 11 (8) ◽  
pp. 741
Author(s):  
Katherine Hicks-Courant ◽  
Jenny Shen ◽  
Angela Stroupe ◽  
Angel Cronin ◽  
Elizabeth F. Bair ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Media Coverage ◽  
Disease Risk ◽  
Federal Drug Administration ◽  
Personalized Cancer Medicine ◽  
The Media ◽  
Cancer Medicine ◽  
Media Reports ◽  
Personalized Cancer ◽  
Standard Tests

Background: Given that media coverage can shape healthcare expectations, it is essential that we understand how the media frames “personalized medicine” (PM) in oncology, and whether information about unproven technologies is widely disseminated. Methods: We conducted a content analysis of 396 news reports related to cancer and PM published between 1 January 1998 and 31 December 2011. Two coders independently coded all the reports using a pre-defined framework. Determination of coverage of “standard” and “non-standard” therapies and tests was made by comparing the media print/broadcast date to the date of Federal Drug Administration approval or incorporation into clinical guidelines. Results: Although the term “personalized medicine” appeared in all reports, it was clearly defined only 27% of the time. Stories more frequently reported PM benefits than challenges (96% vs. 48%, p < 0.001). Commonly reported benefits included improved treatment (89%), prediction of side effects (30%), disease risk prediction (33%), and lower cost (19%). Commonly reported challenges included high cost (28%), potential for discrimination (29%), and concerns over privacy and regulation (21%). Coverage of inherited DNA testing was more common than coverage of tumor testing (79% vs. 25%, p < 0.001). Media reports of standard tests and treatments were common; however, 8% included information about non-standard technologies, such as experimental medications and gene therapy. Conclusion: Confusion about personalized cancer medicine may be exacerbated by media reports that fail to clearly define the term. While most media stories reported on standard tests and treatments, an emphasis on the benefits of PM may lead to unrealistic expectations for cancer genomic care.

scholarly journals Novel Roles for the Sirtuin Deacylase SIRT5 in Normal Physiology and in Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 741-741
Author(s):  
David Lombard
Keyword(s):  
Mitochondrial Matrix ◽  
Genomic Integrity ◽  
Biological Functions ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Catalytic Activities ◽  
Cellular Processes ◽  
Specific Cancer ◽  
Cancer Types ◽  
Chromatin Biology

Abstract Sirtuins are NAD+-dependent deacylases that regulate diverse cellular processes such as metabolic homeostasis and genomic integrity. Mammals possess seven sirtuin family members, SIRT1-SIRT7, that display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions. Three sirtuins, SIRT3, SIRT4, and SIRT5, are primarily located in the mitochondrial matrix. SIRT5 is a very inefficient deacetylase, instead removing negatively charged post-translational modifications (succinyl, glutaryl, and malonyl groups) from lysines of its target proteins, in mitochondria and throughout the cell. SIRT5 plays only modest known roles in normal physiology, with its major functions occurring in the heart under stress conditions. In contrast, in specific cancer types, including melanoma, we have identified a major pro-survival role for SIRT5. We have traced this function of SIRT5 to novel roles for this protein in regulating chromatin biology. New insights into mechanisms of SIRT5 action in cancer, and in normal myocardium, will be discussed.

scholarly journals Personalized cancer medicine and the future of pathology

2011 ◽  
Vol 460 (1) ◽  
pp. 3-8 ◽  
Author(s):  
H. Moch ◽  
P. R. Blank ◽  
M. Dietel ◽  
G. Elmberger ◽  
K. M. Kerr ◽  
...  
Keyword(s):  
Personalized Cancer Medicine ◽  
The Future ◽  
Cancer Medicine ◽  
Personalized Cancer

scholarly journals The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody–positive dermatomyositis

Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 650-655 ◽  
Author(s):  
Alexander Oldroyd ◽  
Jamie C Sergeant ◽  
Paul New ◽  
Neil J McHugh ◽  
Zoe Betteridge ◽  
...  
Keyword(s):  
Proportional Hazard ◽  
Adult Onset ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Specific Cancer ◽  
Associated Malignancy ◽  
Cancer Types ◽  
The Uk ◽  
Screening Approaches

Abstract Objectives To characterize the 10 year relationship between anti-transcriptional intermediary factor 1 antibody (anti-TIF1-Ab) positivity and cancer onset in a large UK-based adult DM cohort. Methods Data from anti-TIF1-Ab-positive/-negative adults with verified diagnoses of DM from the UK Myositis Network register were analysed. Each patient was followed up until they developed cancer. Kaplan–Meier methods and Cox proportional hazard modelling were employed to estimate the cumulative cancer incidence. Results Data from 263 DM cases were analysed, with a total of 3252 person-years and a median 11 years of follow-up; 55 (21%) DM cases were anti-TIF1-Ab positive. After 10 years of follow-up, a higher proportion of anti-TIF1-Ab-positive cases developed cancer compared with anti-TIF1-Ab-negative cases: 38% vs 15% [hazard ratio 3.4 (95% CI 2.2, 5.4)]. All the detected malignancy cases in the anti-TIF1-Ab-positive cohort occurred between 3 years prior to and 2.5 years after DM onset. No cancer cases were detected within the following 7.5 years in this group, whereas cancers were detected during this period in the anti-TIF1-Ab-negative cases. Ovarian cancer was more common in the anti-TIF1-Ab-positive vs -negative cohort: 19% vs 2%, respectively (P < 0.05). No anti-TIF1-Ab-positive case <39 years of age developed cancer, compared with 21 (53%) of those ≥39 years of age. Conclusion Anti-TIF1-Ab-positive-associated malignancy occurs exclusively within the 3 year period on either side of DM onset, the risk being highest in those ≥39 years of age. Cancer types differ according to anti-TIF1-Ab status, and this may warrant specific cancer screening approaches.

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