scholarly journals A connectivity signature for glioblastoma

2021 ◽  
Author(s):  
Ling Hai ◽  
Dirk C Hoffmann ◽  
Henriette Mandelbaum ◽  
Ruifan Xie ◽  
Jakob Ito ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Patient Survival ◽  
Tumor Biology ◽  
Glioma Cells ◽  
Therapy Resistance ◽  
Primary Glioblastoma ◽  
High Connectivity ◽  
Neural Tube Development ◽  
The Impact

Tumor cell extensions called tumor microtubes (TMs) in glioma resemble neurites during neurodevelopment and connect glioma cells to a network that has considerable relevance for tumor progression and therapy resistance. The determination of interconnectivity in individual tumors has been challenging and the impact of tumor cell connectivity on patient survival remained unresolved so far. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells was established and clinically validated. Thirty-four of 40 connectivity genes were related to neurogenesis, neural tube development or glioma progression, including the TM-network-relevant GAP43 gene. Astrocytic-like and mesenchymal-like GB cells had the highest connectivity signature scores in scRNA-Seq data of patient-derived xenografts and patient samples. In 230 human GBs, high connectivity correlated with the mesenchymal expression subtype, TP53 wildtype, and with dismal patient survival. CHI3L1 was identified as a robust molecular marker of connectivity. Thus, the connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell connectivity is relevant for patients prognosis, and serves as a robust biomarker that can be used for future clinical trials.

scholarly journals Chemical hybridization of sulfasalazine and dihydroartemisinin promotes brain tumor cell death

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Annemarie Ackermann ◽  
Aysun Çapcı ◽  
Michael Buchfelder ◽  
Svetlana B. Tsogoeva ◽  
Nicolai Savaskan
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cell Viability ◽  
Malignant Tumors ◽  
Glioma Cells ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Tumor Cell Death ◽  
Combinational Treatment ◽  
The Impact

AbstractGliomas are primary brain tumors with still poor prognosis for the patients despite a combination of cytoreduction via surgery followed by a radio-chemotherapy. One strategy to find effective treatment is to combine two different compounds in one hybrid molecule via linker to add to or at best potentiate their impact on malignant cells. Here, we report on the effects of a newly synthesized hybrid of sulfasalazine (SAS) and dihydroartemisinin (DHA), called AC254. In previous studies, both SAS and DHA have already proved to have anti-tumor properties themselves and to have sensitizing respectively potentiating effects on other treatments against malignant tumors. We investigated the impact of individual drugs SAS and DHA, their 1:1 combination and a novel SAS-DHA hybrid compound (AC254) on rodent and human glioma cells. In our study SAS alone showed no or only a mild effect on glioma, whereas DHA led to a significant reduction of cell viability in a dose-dependent manner. Next we compared the efficacy of the hybrid AC254 to the combinational treatment of its parent compounds SAS and DHA. The hybrid was highly efficient in combating glioma cells compared to single treatment strategies regarding cell viability and cell death. Interestingly, AC254 showed a remarkable advantage over the combinational treatment with both parent compounds in most used concentrations. In addition to its reduction of tumor cell viability and induction of cell death, the hybrid AC254 displayed changes in cell cycle and reduction of cell migration. Taken together, these results demonstrate that clinically established compounds such as SAS and DHA can be potentiated in their anti-cancer effects by chemical hybridization. Thus, this concept provides the opportunity to devise new effective chemotherapeutic agents.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Assessment of sensitivity of the efficiency of regional tax spending towards investment attractiveness of the types of economic activity carried out by the residents of advanced development territory

2020 ◽  
pp. 98-110
Author(s):  
Evgeniya Mikhailovna Popova ◽  
Guzel Mukhtarovna Guseinova ◽  
Sergei Borisovich Milov
Keyword(s):  
Economic Activity ◽  
Socioeconomic Development ◽  
Federal District ◽  
Tax Incentives ◽  
Capital Investments ◽  
The Subject ◽  
Investment Process ◽  
The Impact ◽  
Advanced Development

The deficit of subnational budgets and deceleration capital investments in multiple Russian regions increase the relevance of research aimed at improvement of tax incentivizing practice of the regional investment process. The studies focused on determination of the impact of socioeconomic and institutional factors upon the efficiency of investment tax expenses obtained wide circulation within the foreign scientific literature. The subject of this article is the assessment of sensitivity of the efficiency of regional tax expanses towards investment attractiveness of the types of economic activity carried out by the residents of territories of advanced socioeconomic development, created in the subjects of Far Easter Federal District. The scientific novelty and practical values of this research consists in substantiation of the reasonableness of assessment of investment attractiveness of the types of economic activity that are stimulated by tax incentives. Methodology for assessing investment attractiveness is proposed and tested. The conclusion is made that in case of low investment attractiveness of the type of economic activity, which was planned to support by tax incentives, it is required to conduct and additional analysis to avoid unjustified tax expanses.

Method development for the determination of textural properties of sugar beet roots

2019 ◽  
pp. 392-400 ◽  
Author(s):  
Gunnar Kleuker ◽  
Christa M. Hoffmann
Keyword(s):  
Sugar Beet ◽  
Compression Test ◽  
Storage Period ◽  
Textural Properties ◽  
Small Sample ◽  
Root Tip ◽  
Flexural Test ◽  
Sample Distribution ◽  
The Impact

The harvest of sugar beet leads to root tip breakage and surface damage through mechanical impacts, which increase storage losses. For the determination of textural properties of sugar beet roots with a texture analyzer a reliable method description is missing. This study aimed to evaluate the impact of washing, soil tare, storage period from washing until measurement, sample distribution and number of roots on puncture and compression measurements. For this purpose, in 2017 comprehensive tests were conducted with sugar beet roots grown in a greenhouse. In a second step these tests were carried out with different Beta varieties from a field trial, and in addition, a flexural test was included. Results show that the storage period after washing and the sample distribution had an influence on the puncture and compression strength. It is suggested to wash the roots by hand before the measurement and to determine the strength no later than 48 h after washing. For reliable and comparable results a radial distribution of measurement points around the widest circumference of the root is recommended for the puncture test. The sample position of the compression test had an influence on the compressive strength and therefore, needs to be clearly defined. For the puncture and the compression test it was possible to achieve stable results with a small sample size, but with increasing heterogeneity of the plant stand a higher number of roots is required. The flexural test showed a high variability and is, therefore, not recommended for the analysis of sugar beet textural properties.

Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Canagliflozin and Metformin HCl in Rat Plasma and its Application

2020 ◽  
Vol 16 (6) ◽  
pp. 752-762
Author(s):  
Vivek Nalawade ◽  
Vaibhav A. Dixit ◽  
Amisha Vora ◽  
Himashu Zade
Keyword(s):  
Internal Standard ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Herbal Extracts ◽  
One Step ◽  
Precision And Accuracy ◽  
Development And Validation ◽  
The Impact ◽  
Metformin Hcl

Background: Food and herbal extracts rich in Quercetin (QRT) are often self-medicated by diabetics and can potentially alter the pharmacokinetics (PK) of Metformin HCl (MET) and Canagliflozin (CNG) leading to food or herb-drug interactions and reduced therapeutic efficacy. However, the impact of these flavonoids on the pharmacokinetic behaviour of MET and CNG is mostly unknown. Methods: A simple one-step protein precipitation method was developed for the determination of MET and CNG from rat plasma. The mobile phase chosen was MeOH 65% and 35% water containing 0.1% formic acid at a flow rate of 1mL/min. Results: The retention time of MET, internal standard (Valsartan) and CNG was 1.83, 6.2 and 8.2 min, respectively. The method was found to be linear in the range of 200 - 8000 ng/mL for CNG and 100 = 4000 ng/ml for MET. Precision and accuracy of the method were below 20% at LLOQ and below 15% for LQC, MQC, and HQC. Conclusion: The method was successfully applied for the determination of PK of MET and CNG by using 100 μL of rat plasma. QRT co-administration affects the PK parameters of MET and CNG. This alteration in PK parameters might be of significant use for clinicians and patients.

The Microeconomics of Product Innovation

2018 ◽  
Author(s):  
Paul Stoneman ◽  
Eleonora Bartoloni ◽  
Maurizio Baussola
Keyword(s):  
Product Innovation ◽  
New Products ◽  
Goods And Services ◽  
Product Innovations ◽  
Microeconomic Analysis ◽  
Prime Objective ◽  
Price Measurement ◽  
The Impact

The prime objective of this book is the use microeconomic analysis to guide and provide insight into the generation and adoption of new products. Taking an approach that uses minimal formal mathematics, the volume initially addresses questions of definitions, sources, and extent of product innovation, differentiating between goods and services; hard and soft innovations; horizontal and vertical innovations; original, new to market, and new to firm innovations. The sources of product innovations (e.g. R&D, design, and creativity) are explored empirically, and the extent of such innovations is then pursued using survey and other data. Three chapters are devoted to the theoretical analysis of the demand for and supply of new products and to the determination of firms’ decisions to undertake product innovation. Later chapters encompass empirical evidence on the determination of the extent of product innovation, the diffusion of such innovation, the impact of product innovation on firm performance, price measurement, and welfare, while the final chapter addresses policy issues.

scholarly journals Viscoelastometry for detecting oral anticoagulants

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Philipp Groene ◽  
Daniela Wagner ◽  
Tobias Kammerer ◽  
Lars Kellert ◽  
Andreas Giebl ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Prospective Observational Study ◽  
Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Clotting Time ◽  
Emergency Situations ◽  
Tissue Plasminogen ◽  
The Impact

Abstract Background Determination of anticoagulant therapy is of pronounced interest in emergency situations. However, routine tests do not provide sufficient insight. This study was performed to investigate the impact of anticoagulants on the results of viscoelastometric assays using the ClotPro device. Methods This prospective, observational study was conducted in patients receiving dabigatran, factor Xa (FXa)-inhibitors, phenprocoumon, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (local ethics committee approval number: 17–525-4). Healthy volunteers served as controls. Viscoelastometric assays were performed, including the extrinsic test (EX-test), intrinsic test (IN-test) Russel’s viper venom test (RVV-test), ecarin test (ECA-test), and the tissue plasminogen activator test (TPA-test). Results 70 patients and 10 healthy volunteers were recruited. Clotting time in the EX-test (CTEX-test) was significantly prolonged versus controls by dabigatran, FXa inhibitors and phenprocoumon. CTIN-test was prolonged by dabigatran, FXa inhibitors and UFH. Dabigatran, FXa inhibitors and UFH significantly prolonged CTRVV-test in comparison with controls (median 200, 207 and 289 vs 63 s, respectively; all p < 0.0005). Only dabigatran elicited a significant increase in CTECA-test compared to controls (median 307 vs 73 s; p < 0.0001). CTECA-test correlated strongly with dabigatran plasma concentration (measured by anti-IIa activity; r = 0.9970; p < 0.0001) and provided 100% sensitivity and 100% specificity for detecting dabigatran. Plasma concentrations (anti-XA activity) of FXa inhibitors correlated with CTRVV-test (r = 0.7998; p < 0.0001), and CTRVV-test provided 83% sensitivity and 64% specificity for detecting FXa inhibitors. Conclusions In emergency situations, ClotPro viscoelastometric assessment of whole-blood samples may help towards determining the presence and type of anticoagulant class that a patient is taking. Trial registration German clinical trials database ID: DRKS00015302.

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