scholarly journals Use of amantadine in the evaluation of response to chemotherapy in lung cancer: a pilot study

2021 ◽  
pp. FSO679
Author(s):  
Andrew W Maksymiuk ◽  
Paramjit S Tappia ◽  
Rashid Ahmed Bux ◽  
Dante Moyer ◽  
Guoyu Huang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Large Scale ◽  
Response To Therapy ◽  
Therapeutic Interventions ◽  
Response To Treatment ◽  
Patient Response ◽  
Disease Response ◽  
Early Evaluation ◽  
Response To Chemotherapy

Aim: The assessment of tumor response to therapy is of critical importance as it permits for a prospective end point evaluation and provides a guide to clinicians for making future treatment decisions. However, current practices in early evaluation of chemotherapy are insufficient. Amantadine is a substrate for SSAT-1. The present pilot study tests the hypothesis that SSAT-1 activity within the tumor, as measured by plasma acetylamantadine concentrations, can be used to monitor patient response to therapy. Results: In cases with evidence of disease response, there was a reduction in the plasma acetylamantadine concentration at 4 h by approximately 32%. There was a mean increase of approximately 34% at the 4 h collection in the nonresponders. Conclusion: Although large-scale studies are required these findings suggest that the amantadine test could allow for determination of the efficacy of therapeutic interventions earlier, providing an effective test to assess response to treatment and for better management of patients.

scholarly journals The Potential Role of Genomic Medicine in the Therapeutic Management of Rheumatoid Arthritis

2019 ◽  
Vol 8 (6) ◽  
pp. 826 ◽  
Author(s):  
Marialbert Acosta-Herrera ◽  
David González-Serna ◽  
Javier Martín
Keyword(s):  
Rheumatoid Arthritis ◽  
Large Scale ◽  
Rare Variants ◽  
Drug Repositioning ◽  
Genomic Medicine ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Genomic Studies ◽  
The Right

During the last decade, important advances have occurred regarding understanding of the pathogenesis and treatment of rheumatoid arthritis (RA). Nevertheless, response to treatment is not universal, and choosing among different therapies is currently based on a trial and error approach. The specific patient’s genetic background influences the response to therapy for many drugs: In this sense, genomic studies on RA have produced promising insights that could help us find an effective therapy for each patient. On the other hand, despite the great knowledge generated regarding the genetics of RA, most of the investigations performed to date have focused on identifying common variants associated with RA, which cannot explain the complete heritability of the disease. In this regard, rare variants could also contribute to this missing heritability as well as act as biomarkers that help in choosing the right therapy. In the present article, different aspects of genetics in the pathogenesis and treatment of RA are reviewed, from large-scale genomic studies to specific rare variant analyses. We also discuss the shared genetic architecture existing among autoimmune diseases and its implications for RA therapy, such as drug repositioning.

scholarly journals Determination of Robust Regional CT Radiomics Features for COVID-19

2020 ◽  
Author(s):  
Mahbubunnabi Tamal
Keyword(s):  
Pleural Effusion ◽  
Ground Glass Opacity ◽  
Ct Images ◽  
Accurate Diagnosis ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Z Score ◽  
The Difference ◽  
Severity Of The Disease

ABSTRACTBackgroundThe lung CT images of COVID-19 patients can be characterized by three different regions – Ground Glass Opacity (GGO), consolidation and pleural effusion. GCOs have been shown to precede consolidations. Quantitative characterization of these regions using radiomics can facilitate accurate diagnosis, disease progression and response to treatment. However, according to the knowledge of the author, regional CT radiomics analysis of COVID-19 patients has not been carried out. This study aims to address these by determining the radiomics features that can characterize each of the regions separately and can distinguish the regions from each other.Methods44 radiomics features were generated with four quantization levels for 23 CT slice of 17 patients. Two approaches were the implemented to determine the features that can differentiate between lung regions – 1) Z-score and correlation heatmaps and 2) one way ANOVA for finding statistically significantly difference (p<0.05) between the regions. Radiomics features that show agreement for all cases (Z-score, correlation and statistical significant test) were selected as suitable features. The features were then tested on 52 CT images.Results10 radiomics features were found to be the most suitable among 44 features. When applied on the test images, they can differentiate between GCO, consolidation and pleural effusion successfully and the difference provided by these 10 features between three lung regions are statistically significant.ConclusionThe ten robust radiomics features can be useful in extracting quantitative data from CT lung images to characterize the disease in the patient, which in turn can help in more accurate diagnosis, staging the severity of the disease and allow the clinician to plan for more successful personalized treatment for COVID-19 patients. They can also be used for monitoring the progression of COVID-19 and response to therapy for clinical trials.

scholarly journals Large-Scale Transcriptomics-Driven Approach Revealed Overexpression of CRNDE as a Poor Survival Prognosis Biomarker in Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3419
Author(s):  
Maxim Sorokin ◽  
Mikhail Raevskiy ◽  
Alja Zottel ◽  
Neja Šamec ◽  
Marija Skoblar Vidmar ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Disease Diagnosis ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Survival Prognosis ◽  
Tissue Samples ◽  
Patient Response ◽  
Genome Atlas

Glioblastoma is the most common and malignant brain malignancy worldwide, with a 10-year survival of only 0.7%. Aggressive multimodal treatment is not enough to increase life expectancy and provide good quality of life for glioblastoma patients. In addition, despite decades of research, there are no established biomarkers for early disease diagnosis and monitoring of patient response to treatment. High throughput sequencing technologies allow for the identification of unique molecules from large clinically annotated datasets. Thus, the aim of our study was to identify significant molecular changes between short- and long-term glioblastoma survivors by transcriptome RNA sequencing profiling, followed by differential pathway-activation-level analysis. We used data from the publicly available repositories The Cancer Genome Atlas (TCGA; number of annotated cases = 135) and Chinese Glioma Genome Atlas (CGGA; number of annotated cases = 218), and experimental clinically annotated glioblastoma tissue samples from the Institute of Pathology, Faculty of Medicine in Ljubljana corresponding to 2–58 months overall survival (n = 16). We found one differential gene for long noncoding RNA CRNDE whose overexpression showed correlation to poor patient OS. Moreover, we identified overlapping sets of congruently regulated differential genes involved in cell growth, division, and migration, structure and dynamics of extracellular matrix, DNA methylation, and regulation through noncoding RNAs. Gene ontology analysis can provide additional information about the function of protein- and nonprotein-coding genes of interest and the processes in which they are involved. In the future, this can shape the design of more targeted therapeutic approaches.

Large-scale Motion of Solar Filaments

2000 ◽  
Vol 179 ◽  
pp. 205-208
Author(s):  
Pavel Ambrož ◽  
Alfred Schroll
Keyword(s):  
Magnetic Flux ◽  
Proper Motion ◽  
Time Scale ◽  
Large Scale ◽  
Accuracy Of Measurements ◽  
Solar Filaments ◽  
General Movement ◽  
Scale Motion ◽  
Velocity Scatter

AbstractPrecise measurements of heliographic position of solar filaments were used for determination of the proper motion of solar filaments on the time-scale of days. The filaments have a tendency to make a shaking or waving of the external structure and to make a general movement of whole filament body, coinciding with the transport of the magnetic flux in the photosphere. The velocity scatter of individual measured points is about one order higher than the accuracy of measurements.

Studies on the Fibrinolytic System in Human Plasma: Quantitative Determination of Plasminogen Activators and Proactivators

1979 ◽  
Vol 41 (02) ◽  
pp. 365-383 ◽  
Author(s):  
C Kluft
Keyword(s):  
Pilot Study ◽  
Plasma Level ◽  
Human Plasma ◽  
Plasminogen Activators ◽  
Venous Occlusion ◽  
Quantitative Information ◽  
Optimal Recovery ◽  
Dextran Sulphate ◽  
Baseline Levels

SummaryEffects due to plasma plasminogen activators and proactivators are usually studied in assay systems where inhibitors influence the activity and where the degree of activation of proactivators is unknown. Quantitative information on activator and proactivator levels in plasma is therefore not availableStudies on the precipitating and activating properties of dextran sulphate in euglobulin fractionation presented in this paper resulted in the preparation of a fraction in which there was optimal recovery and optimal activation of a number of plasminogen activators and proactivators from human plasma. The quantitative assay of these activators on plasminogen-rich fibrin plates required the addition of flufenamate to eliminate inhibitors. The response on the fibrin plates (lysed zones) could be coverted to arbitrary blood activator units (BAU). Consequently, a new activator assay which enables one to quantitatively determine the plasma level of plasminogen activators and proactivators together is introduced.Two different contributions could be distinguished: an activity originating from extrinsic activator and one originating from intrinsic proactivators. The former could be assayed separately by means of its resistance to inhibition by Cl-inactivator. Considering the relative concentrations of extrinsic and intrinsic activators, an impression of the pattern of activator content in plasma was gained. In morning plasma with baseline levels of fibrinolysis, the amount of extrinsic activator was negligible as compared to the level of potentially active intrinsic activators. Consequently, the new assay nearly exclusively determines the level of intrinsic activators in morning plasma. A pilot study gave a fairly stable level of 100 ± 15 BAU/ml (n = 50). When fibrinolysis was stimulated by venous occlusion (15 min), the amount of extrinsic activator was greatly increased, reaching a total activator level of 249 ± 27 BAU/ml (n = 7).

Methods for the Quantification of Salivary Cortisol and of a-amylase in Biosensors and Portable Devices

2018 ◽  
Vol 68 (12) ◽  
pp. 2857-2859
Author(s):  
Cristina Mihaela Ghiciuc ◽  
Andreea Silvana Szalontay ◽  
Luminita Radulescu ◽  
Sebastian Cozma ◽  
Catalina Elena Lupusoru ◽  
...  
Keyword(s):  
Real Time ◽  
Medical Practice ◽  
Salivary Cortisol ◽  
Clinical Studies ◽  
Large Scale ◽  
Psychological Research ◽  
Portable Devices ◽  
Salivary Amylase ◽  
Specificity And Sensitivity

There is an increasing interest in the analysis of salivary biomarkers for medical practice. The objective of this article was to identify the specificity and sensitivity of quantification methods used in biosensors or portable devices for the determination of salivary cortisol and salivary a-amylase. There are no biosensors and portable devices for salivary amylase and cortisol that are used on a large scale in clinical studies. These devices would be useful in assessing more real-time psychological research in the future.

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

2019 ◽  
Vol 22 (5) ◽  
pp. 346-354
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Large Scale ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
Reporter System ◽  
E Coli ◽  
Starting Point ◽  
High Concentrations ◽  
Mic Value

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

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