scholarly journals A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs

2021 ◽  
Author(s):  
Alexandre Bordat ◽  
Tanguy Boissenot ◽  
Nada Ibrahim ◽  
Marianne Ferrere ◽  
Manon Levêque ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Release Kinetics ◽  
Hydrophilic Polymer ◽  
Case Scenario ◽  
Worst Case ◽  
Anticancer Efficacy ◽  
Local Toxicity ◽  
Two Factors ◽  
Hospital Stays

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections). Therefore, the development of effective and less costly chemotherapy that is more comfortable for the patient would revolutionize cancer therapy. While subcutaneous (SC) administration has the potential to meet these criteria, it is extremely restrictive as it cannot be applied to most anticancer drugs, such as irritant or vesicant ones, for local toxicity reasons. Herein, we report a facile, general and scalable approach for the SC administration of anticancer drugs through the design of well-defined hydrophilic polymer prodrugs. This was applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario due to its high hydrophobicity and vesicant properties (two factors promoting necrosis at the injection site), whereas polyacrylamide (PAAm) was chosen as a hydrophilic polymer for its biocompatibility and stealth properties. A small library of Ptx-based polymer prodrugs was designed by adjusting the nature of the linker (ester, diglycolate and carbonate), and then evaluated in terms of rheological/viscosity properties in aqueous solutions, drug release kinetics in PBS and in murine plasma, cytotoxicity on two different cancer cell lines, acute local and systemic toxicity, pharmacokinetics and biodistribution, and finally their anticancer efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be safely injected subcutaneously without inducing local toxicity while outperforming Taxol, the commercial formulation of Ptx, thus opening the door to the safe transposition from IV to SC chemotherapy.

scholarly journals A Polymer Prodrug Strategy to Switch from Intravenous to Subcutaneous Cancer Therapy for Irritant/Vesicant Drugs

2021 ◽  
Author(s):  
Alexandre Bordat ◽  
Tanguy Boissenot ◽  
Nada Ibrahim ◽  
Marianne Ferrere ◽  
Manon Levêque ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Release Kinetics ◽  
Hydrophilic Polymer ◽  
Case Scenario ◽  
Worst Case ◽  
Anticancer Efficacy ◽  
Local Toxicity ◽  
Two Factors ◽  
Hospital Stays

Chemotherapy is almost exclusively administered via the intravenous (IV) route, which has serious limitations (e.g., patient discomfort, long hospital stays, need for trained staff, high cost, catheter failures, infections). Therefore, the development of effective and less costly chemotherapy that is more comfortable for the patient would revolutionize cancer therapy. While subcutaneous (SC) administration has the potential to meet these criteria, it is extremely restrictive as it cannot be applied to most anticancer drugs, such as irritant or vesicant ones, for local toxicity reasons. Herein, we report a facile, general and scalable approach for the SC administration of anticancer drugs through the design of well-defined hydrophilic polymer prodrugs. This was applied to the anticancer drug paclitaxel (Ptx) as a worst-case scenario due to its high hydrophobicity and vesicant properties (two factors promoting necrosis at the injection site), whereas polyacrylamide (PAAm) was chosen as a hydrophilic polymer for its biocompatibility and stealth properties. A small library of Ptx-based polymer prodrugs was designed by adjusting the nature of the linker (ester, diglycolate and carbonate), and then evaluated in terms of rheological/viscosity properties in aqueous solutions, drug release kinetics in PBS and in murine plasma, cytotoxicity on two different cancer cell lines, acute local and systemic toxicity, pharmacokinetics and biodistribution, and finally their anticancer efficacy. We demonstrated that Ptx-PAAm polymer prodrugs could be safely injected subcutaneously without inducing local toxicity while outperforming Taxol, the commercial formulation of Ptx, thus opening the door to the safe transposition from IV to SC chemotherapy.

Reducing Probabilistic Weather Forecasts to the Worst Case Scenario: Anchoring Effects

2008 ◽  
Author(s):  
Sonia Savelli ◽  
Susan Joslyn ◽  
Limor Nadav-Greenberg ◽  
Queena Chen
Keyword(s):  
Case Scenario ◽  
Worst Case ◽  
Weather Forecasts ◽  
Worst Case Scenario ◽  
Anchoring Effects

ROLE OF ADDED PHOSPHOGYPSUM AND HUMIC ACIDS IN THE KINETIC RELEASE OF SALT FROM SALT AFFECTED SOIL (SALINE – SODIC)

2020 ◽  
pp. 15-27
Keyword(s):  
Electrical Conductivity ◽  
Humic Acids ◽  
Release Rate ◽  
Release Kinetics ◽  
Sodium Adsorption Ratio ◽  
Salt Affected Soil ◽  
Two Factors ◽  
Dissolved Ions ◽  
Kinetic Release

In order to study the effect of phosphogypsum and humic acids in the kinetic release of salt from salt-affected soil, a laboratory experiment was conducted in which columns made from solid polyethylene were 60.0 cm high and 7.1 cm in diameter. The columns were filled with soil so that the depth of the soil was 30 cm inside the column, the experiment included two factors, the first factor was phosphogypsum and was added at levels 0, 5, 10 and 15 tons ha-1 and the second-factor humic acids were added at levels 0, 50, 100 and 150 kg ha-1 by mixing them with the first 5 cm of column soil and one repeater per treatment. The continuous leaching method was used by using an electrolytic well water 2.72 dS m-1. Collect the leachate daily and continue the leaching process until the arrival of the electrical conductivity of the filtration of leaching up to 3-5 dS m-1. The electrical conductivity and the concentration of positive dissolved ions (Ca, Mg, Na) were estimated in leachate and the sodium adsorption ratio (SAR) was calculated. The results showed that the best equation for describing release kinetics of the salts and sodium adsorption ratio in soil over time is the diffusion equation. Increasing the level of addition of phosphogypsum and humic acids increased the constant release velocity (K) of salts and the sodium adsorption ratio. The interaction between phosphogypsum and humic acids was also affected by the constant release velocity of salts and the sodium adsorption ratio. The constant release velocity (K) of the salts and the sodium adsorption ratio at any level of addition of phosphogypsum increased with the addition of humic acids. The highest salts release rate was 216.57 in PG3HA3, while the lowest rate was 149.48 in PG0HA0. The highest release rate of sodium adsorption ratio was 206.09 in PG3HA3, while the lowest rate was 117.23 in PG0HA0.

EXPEDITION TO MALI, 2020

2020 ◽  
pp. 12-28
Author(s):  
D. V. Vaniukova ◽  
◽  
P. A. Kutsenkov ◽  
Keyword(s):  
Mass Murder ◽  
The State ◽  
Case Scenario ◽  
Worst Case ◽  
Traditional Art ◽  
Peter The Great ◽  
State Museum ◽  
Bobo Dioulasso ◽  
Oriental Studies ◽  
The Village

The research expedition of the Institute of Oriental studies of the Russian Academy of Sciences has been working in Mali since 2015. Since 2017, it has been attended by employees of the State Museum of the East. The task of the expedition is to study the transformation of traditional Dogon culture in the context of globalization, as well as to collect ethnographic information (life, customs, features of the traditional social and political structure); to collect oral historical legends; to study the history, existence, and transformation of artistic tradition in the villages of the Dogon Country in modern conditions; collecting items of Ethnography and art to add to the collection of the African collection of the. Peter the Great Museum (Kunstkamera, Saint Petersburg) and the State Museum of Oriental Arts (Moscow). The plan of the expedition in January 2020 included additional items, namely, the study of the functioning of the antique market in Mali (the “path” of things from villages to cities, which is important for attributing works of traditional art). The geography of our research was significantly expanded to the regions of Sikasso and Koulikoro in Mali, as well as to the city of Bobo-Dioulasso and its surroundings in Burkina Faso, which is related to the study of migrations to the Bandiagara Highlands. In addition, the plan of the expedition included organization of a photo exhibition in the Museum of the village of Endé and some educational projects. Unfortunately, after the mass murder in March 2019 in the village of Ogossogou-Pel, where more than one hundred and seventy people were killed, events in the Dogon Country began to develop in the worst-case scenario: The incessant provocations after that revived the old feud between the Pel (Fulbe) pastoralists and the Dogon farmers. So far, this hostility and mutual distrust has not yet developed into a full-scale ethnic conflict, but, unfortunately, such a development now seems quite likely.

Risk-Based Robust Bidding Strategies for EVs’ Aggregators in Day-ahead Markets with Uncertainty

2020 ◽  
Author(s):  
Ahmed Abdelmoaty ◽  
Wessam Mesbah ◽  
Mohammad A. M. Abdel-Aal ◽  
Ali T. Alawami
Keyword(s):  
Robust Optimization ◽  
Electricity Market ◽  
Real Life ◽  
Optimization Approach ◽  
Case Scenario ◽  
Worst Case ◽  
Bidding Strategies ◽  
Wind Generators ◽  
Proposed Model ◽  
Optimal Bidding

In the recent electricity market framework, the profit of the generation companies depends on the decision of the operator on the schedule of its units, the energy price, and the optimal bidding strategies. Due to the expanded integration of uncertain renewable generators which is highly intermittent such as wind plants, the coordination with other facilities to mitigate the risks of imbalances is mandatory. Accordingly, coordination of wind generators with the evolutionary Electric Vehicles (EVs) is expected to boost the performance of the grid. In this paper, we propose a robust optimization approach for the coordination between the wind-thermal generators and the EVs in a virtual<br>power plant (VPP) environment. The objective of maximizing the profit of the VPP Operator (VPPO) is studied. The optimal bidding strategy of the VPPO in the day-ahead market under uncertainties of wind power, energy<br>prices, imbalance prices, and demand is obtained for the worst case scenario. A case study is conducted to assess the e?effectiveness of the proposed model in terms of the VPPO's profit. A comparison between the proposed model and the scenario-based optimization was introduced. Our results confirmed that, although the conservative behavior of the worst-case robust optimization model, it helps the decision maker from the fluctuations of the uncertain parameters involved in the production and bidding processes. In addition, robust optimization is a more tractable problem and does not suffer from<br>the high computation burden associated with scenario-based stochastic programming. This makes it more practical for real-life scenarios.<br>

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

Design of Lamivudine Loaded Nanoparticles for Oral Application by Nano Spray Drying Method: A New Approach to use an Antiretroviral Drug for Lung Cancer Treatment

2020 ◽  
Vol 23 (10) ◽  
pp. 1064-1079
Author(s):  
Ahmet Alper Öztürk ◽  
İrem Namlı ◽  
Kadri Güleç ◽  
Şennur Görgülü
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Cell Line ◽  
Anticancer Drugs ◽  
Release Kinetics ◽  
Prolonged Release ◽  
Lung Cancer Treatment ◽  
Anticancer Properties ◽  
Ft Ir

Aims: To prepare lamivudine (LAM)-loaded-nanoparticles (NPs) that can be used in lung cancer treatment. To change the antiviral indication of LAM to anticancer. Background: The development of anticancer drugs is a difficult process. One approach to accelerate the availability of drugs is to reclassify drugs approved for other conditions as anticancer. The most common route of administration of anticancer drugs is intravenous injection. Oral administration of anticancer drugs may considerably change current treatment modalities of chemotherapy and improve the life quality of cancer patients. There is also a potentially significant economic advantage. Objective: To characterize the LAM-loaded-NPs and examine the anticancer activity. Methods: LAM-loaded-NPs were prepared using Nano Spray-Dryer. Properties of NPs were elucidated by particle size (PS), polydispersity index (PDI), zeta potential (ZP), SEM, encapsulation efficiency (EE%), dissolution, release kinetics, DSC and FT-IR. Then, the anticancer activity of all NPs was examined. Results: The PS values of the LAM-loaded-NPs were between 373 and 486 nm. All NPs prepared have spherical structure and positive ZP. EE% was in a range of 61-79%. NPs showed prolonged release and the release kinetics fitted to the Weibull model. NPs structures were clarified by DSC and FT-IR analysis. The results showed that the properties of NPs were directly related to the drug:polymer ratio of feed solution. NPs have potential anticancer properties against A549 cell line at low concentrations and non-toxic to CCD 19-Lu cell line. Conclusion: NPs have potential anticancer properties against human lung adenocarcinoma cells and may induce cell death effectively and be a potent modality to treat this type of cancer. These experiments also indicate that our formulations are non-toxic to normal cells. It is clear that this study would bring a new perspective to cancer therapy.

scholarly journals A Thermally Conductive Pt/AAO Catalyst for Hydrogen Passive Autocatalytic Recombination

Catalysts ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 491
Author(s):  
Alina E. Kozhukhova ◽  
Stephanus P. du Preez ◽  
Aleksander A. Malakhov ◽  
Dmitri G. Bessarabov
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Combustion Temperature ◽  
Volume Fraction ◽  
Morphological Characteristics ◽  
Al Alloy ◽  
Impregnation Method ◽  
Case Scenario ◽  
Worst Case ◽  
Thermal Distribution

In this study, a Pt/anodized aluminum oxide (AAO) catalyst was prepared by the anodization of an Al alloy (Al6082, 97.5% Al), followed by the incorporation of Pt via an incipient wet impregnation method. Then, the Pt/AAO catalyst was evaluated for autocatalytic hydrogen recombination. The Pt/AAO catalyst’s morphological characteristics were determined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The average Pt particle size was determined to be 3.0 ± 0.6 nm. This Pt/AAO catalyst was tested for the combustion of lean hydrogen (0.5–4 vol% H2 in the air) in a recombiner section testing station. The thermal distribution throughout the catalytic surface was investigated at 3 vol% hydrogen (H2) using an infrared camera. The Al/AAO system had a high thermal conductivity, which prevents the formation of hotspots (areas where localized surface temperature is higher than an average temperature across the entire catalyst surface). In turn, the Pt stability was enhanced during catalytic hydrogen combustion (CHC). A temperature gradient over 70 mm of the Pt/AAO catalyst was 23 °C and 42 °C for catalysts with uniform and nonuniform (worst-case scenario) Pt distributions. The commercial computational fluid dynamics (CFD) code STAR-CCM+ was used to compare the experimentally observed and numerically simulated thermal distribution of the Pt/AAO catalyst. The effect of the initial H2 volume fraction on the combustion temperature and conversion of H2 was investigated. The activation energy for CHC on the Pt/AAO catalyst was 19.2 kJ/mol. Prolonged CHC was performed to assess the durability (reactive metal stability and catalytic activity) of the Pt/AAO catalyst. A stable combustion temperature of 162.8 ± 8.0 °C was maintained over 530 h of CHC. To confirm that Pt aggregation was avoided, the Pt particle size and distribution were determined by TEM before and after prolonged CHC.

scholarly journals Bioinformatic Analysis of the Nicotinamide Binding Site in Poly(ADP-Ribose) Polymerase Family Proteins

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1201
Author(s):  
Garri Manasaryan ◽  
Dmitry Suplatov ◽  
Sergey Pushkarev ◽  
Viktor Drobot ◽  
Alexander Kuimov ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Binding Site ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioinformatic Analysis ◽  
Parp Inhibitors ◽  
Functional Region ◽  
D Loop

The PARP family consists of 17 members with diverse functions, including those related to cancer cells’ viability. Several PARP inhibitors are of great interest as innovative anticancer drugs, but they have low selectivity towards distinct PARP family members and exert serious adverse effects. We describe a family-wide study of the nicotinamide (NA) binding site, an important functional region in the PARP structure, using comparative bioinformatic analysis and molecular modeling. Mutations in the NA site and D-loop mobility around the NA site were identified as factors that can guide the design of selective PARP inhibitors. Our findings are of particular importance for the development of novel tankyrase (PARPs 5a and 5b) inhibitors for cancer therapy.

scholarly journals A Comparison of Match Demands Using Ball-in-Play versus Whole Match Data in Professional Soccer Players of the English Championship

Sports ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 76
Author(s):  
Dylan Mernagh ◽  
Anthony Weldon ◽  
Josh Wass ◽  
John Phillips ◽  
Nimai Parmar ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Soccer Players ◽  
Training Methods ◽  
Case Scenario ◽  
Worst Case ◽  
Repeated Measures Design ◽  
Worst Case Scenario ◽  
Professional Soccer ◽  
Peak Match ◽  
Playing Time

This is the first study to report the whole match, ball-in-play (BiP), ball-out-of-play (BoP), and Max BiP (worst case scenario phases of play) demands of professional soccer players competing in the English Championship. Effective playing time per soccer game is typically <60 min. When the ball is out of play, players spend time repositioning themselves, which is likely less physically demanding. Consequently, reporting whole match demands may under-report the physical requirements of soccer players. Twenty professional soccer players, categorized by position (defenders, midfielders, and forwards), participated in this study. A repeated measures design was used to collect Global Positioning System (GPS) data over eight professional soccer matches in the English Championship. Data were divided into whole match and BiP data, and BiP data were further sub-divided into different time points (30–60 s, 60–90 s, and >90 s), providing peak match demands. Whole match demands recorded were compared to BiP and Max BiP, with BiP data excluding all match stoppages, providing a more precise analysis of match demands. Whole match metrics were significantly lower than BiP metrics (p < 0.05), and Max BiP for 30–60 s was significantly higher than periods between 60–90 s and >90 s. No significant differences were found between positions. BiP analysis allows for a more accurate representation of the game and physical demands imposed on professional soccer players. Through having a clearer understanding of maximum game demands in professional soccer, practitioners can design more specific training methods to better prepare players for worst case scenario passages of play.

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