scholarly journals Novel weapon to conquer human glioblastoma: G-quadruplexes and neuro-inducers

2021 ◽  
Author(s):  
Galina Pavlova ◽  
Varvara Kolesnikova ◽  
Nadezhda Samoylenkova ◽  
Sergey Drozd ◽  
Alexander Revishchin ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cell Cultures ◽  
Tumor Tissue ◽  
Therapy Resistance ◽  
Cell Reprogramming ◽  
Tumor Resistance ◽  
New Approach ◽  
Promising Strategy ◽  
Glioblastoma Recurrence ◽  
Different Response

Abstract Cancer cell reprogramming based on aptamers with antiproliferative properties in combination with small molecules that are used for conversion iPSCs into neurons represents a new approach to reduce the probability of glioblastoma recurrence and tumor resistance to therapy. In this research we tested several combinations of factors on whole cell cultures, derived from tumor tissue after surgical resection, and on cell cultures divided in CD133 enriched and depleted populations, as CD133 marker is believed to be characteristic for glioblastoma stem cells. We showed that CD133+ and CD133- cells have a different response to tested combinations of factors and CD133-positive cells are more stable and possess stemness properties. Thus, affecting these cells will lead to decrease of therapy resistance. Moreover, we found a combination of factors that is able to inhibit proliferation of both CD133+ and CD133- cells. Our results reveal a promising strategy to improve treatment of patients with glioblastoma.

scholarly journals Novel weapon to conquer human glioblastoma: G-quadruplexes and neuro-inducers

2021 ◽  
Author(s):  
Galina Pavlova ◽  
Varvara Kolesnikova ◽  
Nadezhda Samoylenkova ◽  
Sergey Drozd ◽  
Alexander Revishchin ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cell Cultures ◽  
Tumor Tissue ◽  
Therapy Resistance ◽  
Cell Reprogramming ◽  
Tumor Resistance ◽  
New Approach ◽  
Promising Strategy ◽  
Glioblastoma Recurrence ◽  
Different Response

Abstract Cancer cell reprogramming based on aptamers with antiproliferative properties in combination with small molecules that are used for conversion iPSCs into neurons represents a new approach to reduce the probability of glioblastoma recurrence and tumor resistance to therapy. In this research we tested several combinations of factors on whole cell cultures, derived from tumor tissue after surgical resection, and on cell cultures divided in CD133 enriched and depleted populations, as CD133 marker is believed to be characteristic for glioblastoma stem cells. We showed that CD133+ and CD133- cells have a different response to tested combinations of factors and CD133-positive cells are more stable and possess stemness properties. Thus, affecting these cells will lead to decrease of therapy resistance. Moreover, we found a combination of factors that is able to inhibit proliferation of both CD133+ and CD133- cells. Our results reveal a promising strategy to improve treatment of patients with glioblastoma.

scholarly journals Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 403
Author(s):  
Luiz F. S. Oliveira ◽  
Danilo Predes ◽  
Helena L. Borges ◽  
Jose G. Abreu
Keyword(s):  
Colorectal Cancer ◽  
Small Molecules ◽  
Tumor Tissue ◽  
Patient Survival ◽  
Therapeutic Potential ◽  
Antitumor Activities ◽  
The Past ◽  
Naturally Occurring ◽  
Promising Strategy ◽  
Antitumor Properties

Colorectal cancer (CRC) ranks second in the number of cancer deaths worldwide, mainly due to late diagnoses, which restrict treatment in the potentially curable stages and decrease patient survival. The treatment of CRC involves surgery to remove the tumor tissue, in addition to radiotherapy and systemic chemotherapy sessions. However, almost half of patients are resistant to these treatments, especially in metastatic cases, where the 5-year survival rate is only 12%. This factor may be related to the intratumoral heterogeneity, tumor microenvironment (TME), and the presence of cancer stem cells (CSCs), which is impossible to resolve with the standard approaches currently available in clinical practice. CSCs are APC-deficient, and the search for alternative therapeutic agents such as small molecules from natural sources is a promising strategy, as these substances have several antitumor properties. Many of those interfere with the regulation of signaling pathways at the central core of CRC development, such as the Wnt/β-catenin, which plays a crucial role in the cell proliferation and stemness in the tumor. This review will discuss the use of naturally occurring small molecules inhibiting the Wnt/β-catenin pathway in experimental CRC models over the past decade, highlighting the molecular targets in the Wnt/β-catenin pathway and the mechanisms through which these molecules perform their antitumor activities.

Can hydrological model identifiability be improved? Stress-testing the concept of stochastic calibration

2021 ◽  
Author(s):  
Vasileios Kourakos ◽  
Andreas Efstratiadis ◽  
Ioannis Tsoukalas
Keyword(s):  
Dependence Structure ◽  
Hydrological Models ◽  
Proof Of Concept ◽  
Rainfall Runoff ◽  
Predictive Capacity ◽  
New Approach ◽  
Stochastic Inputs ◽  
Promising Strategy ◽  
Synthetic Time Series ◽  
Temporal Windows

<p>Hydrological calibrations with historical data are often deemed insufficient for deducing safe estimations about a model structure that imitates, as closely as possible, the anticipated catchment behaviour. Ιn order to address this issue, we investigate a promising strategy, using as drivers synthetic time series, which preserve the probabilistic properties and dependence structure of the observed data. The key idea is calibrating a model on the basis of synthetic rainfall-runoff data, and validating against the full observed data sample. To this aim, we employed a proof of concept on few representative catchments, by testing several lumped conceptual hydrological models with alternative parameterizations and across two time-scales, monthly and daily. Next, we attempted to reinforce the validity of the recommended methodology by employing monthly stochastic calibrations in 100 MOPEX catchments. As before, a number of different hydrological models were used, for the purpose of proving that calibration with stochastic inputs is independent of the chosen model. The results highlight that in most cases the new approach leads to stronger parameter identifiability and stable predictive capacity across different temporal windows, since the model is trained over much extended hydroclimatic conditions.</p>

scholarly journals Water-in-Water Emulsion as a New Approach to Produce Mesalamine-Loaded Xylan-Based Microparticles

2019 ◽  
Vol 9 (17) ◽  
pp. 3519
Author(s):  
Bartolomeu S. Souza ◽  
Henrique R. Marcelino ◽  
Francisco Alexandrino ◽  
Silvana C. C. Urtiga ◽  
Karen C. H. Silva ◽  
...  
Keyword(s):  
Small Molecules ◽  
Drug Loading ◽  
Continuous Phase ◽  
Clinical Use ◽  
Water Emulsion ◽  
New Approach ◽  
Emulsion Method ◽  
Discontinuous Phase ◽  
Rapid Diffusion ◽  
Full Factorial

The water-in-water emulsion method has been reported as a technique able to prepare microparticles without using harmful solvents. However, there are few reports showing the encapsulation of small molecules into microparticles produced within this technique. The probable reason relays on the rapid diffusion of these molecules from the discontinuous phase to the continuous phase. In the present study, xylan microparticles containing mesalamine were produced and the doubled crosslinking approach, used to promote higher encapsulation rates, was disclosed. To achieve this goal, a 23 full factorial design was carried out. The results revealed that all formulations presented spherical-shaped microparticles. However, at specific conditions, only few formulations reached up to 50% of drug loading. In addition, the new xylan-based microparticles formulation retained almost 40% of its drug content after 12 h of a dissolution assay likely due to the degree of crosslinking. Thus, the doubled crosslinking approach used was effective on the encapsulation of mesalamine and may pave the way to successfully produce other polysaccharide-based carriers for clinical use.

scholarly journals A New Approach to Molecular Configuration Applied to Aqueous Pore Transport

1967 ◽  
Vol 50 (11) ◽  
pp. 2565-2578 ◽  
Author(s):  
Andrew H. Soll
Keyword(s):  
Reflection Coefficient ◽  
Small Molecules ◽  
Structural Characteristic ◽  
Statistical Analyses ◽  
Molecular Models ◽  
Significant Relation ◽  
Molecular Configuration ◽  
New Approach

A cylindrical treatment of the configuration of small molecules in solution has been proposed. Cylindrical dimensions were obtained from Fisher-Hirschfelder molecular models, and these dimensions were used in an analysis of three sets of reflection coefficient values from the literature. The correlation between solute dimensions and the reflection coefficient was subjected to both statistical analyses and graphical examination, with particular emphasis given to parameter interdependence. The results consistently indicated a significant relation between the reflection coefficient and solute diameter. The dependence on diameter suggests a lengthwise orientation of solute within the membrane. Furthermore it is shown that this orientation is occurring within the aqueous region of the membrane, and thus this region has a structural characteristic which is responsible for the lengthwise orientation of solute.

scholarly journals Small Molecules for Cell Reprogramming and Heart Repair: Progress and Perspective

2014 ◽  
Vol 9 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Min Xie ◽  
Nan Cao ◽  
Sheng Ding
Keyword(s):  
Small Molecules ◽  
Cell Reprogramming ◽  
Heart Repair

Combining small molecules for cell reprogramming through an interatomic analysis

2013 ◽  
Vol 9 (11) ◽  
pp. 2741 ◽  
Author(s):  
Bruno César Feltes ◽  
Diego Bonatto
Keyword(s):  
Small Molecules ◽  
Cell Reprogramming

scholarly journals Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation

2021 ◽  
Vol 9 ◽  
Author(s):  
Ming He ◽  
Wenxing Lv ◽  
Yu Rao
Keyword(s):  
Rna Interference ◽  
Protein Degradation ◽  
Small Molecules ◽  
Small Molecule ◽  
Gene Editing ◽  
Small Molecule Inhibitors ◽  
Tumor Resistance ◽  
Target Proteins ◽  
Enzymatic Function ◽  
New Type

Proteolysis targeting chimeras (PROTAC) represents a new type of small molecule induced protein degradation technology that has emerged in recent years. PROTAC uses bifunctional small molecules to induce ubiquitination of target proteins and utilizes intracellular proteasomes for chemical knockdown. It complements the gene editing and RNA interference for protein knockdown. Compared with small molecule inhibitors, PROTAC has shown great advantages in overcoming tumor resistance, affecting the non-enzymatic function of target proteins, degrading undruggable targets, and providing new rapid and reversible chemical knockout tools. At the same time, its challenges and problems also need to be resolved as a fast-developing newchemical biology technology.

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