scholarly journals Growth of mixed cancer cell population – in silico the size matters

2020 ◽  
Author(s):  
Adam Kłóś ◽  
Przemysław M. Płonka
Keyword(s):  
Tumor Growth ◽  
Cell Size ◽  
In Silico ◽  
Small Cells ◽  
Factors Affecting ◽  
Cancer Heterogeneity ◽  
Number Of Cells ◽  
Heterogeneous Tumor

Cancer heterogeneity is still underexplored and difficult to investigate. The whole network of factors engaged in tumor growth makes clinical cases, as well as the in vivo and in vitro experiments of limited use in terms of understanding cancer heterogeneity. Our idea was to start from scratch and focus on the simplest distinctive feature in a heterogeneous tumor, namely the cell size. To exclude any other factors, we created a rudimentary cellular automata model of mixed cancer culture with two lines of different cell sizes. We tested the model with various sets of parameters to explore how the cell size affects cancer co-culture growth. It turned out that the cell size plays a crucial role in in silico heterogeneous tumor growth. The dominance of bigger cells decreases the number of cells in the overall mixed cancer population. In contrast, the small cells increase the total number of cells, even without a parallel enlargement of the macroscopic tumor size. The predominance of the smaller cells is particularly visible in overcrowded conditions. Although our model was primarily designed for verification of experimental hypothesis and as a mean for better understanding of the cancer heterogeneity itself, it is as well of some practical value. Our findings can affect today’s practice of estimating tumor growth based on its macroscopic size and may propose a new approach to interpreting histological data. After modifications, the model may serve to test other factors affecting the growth of mixed populations of cancer cells differing in size.

scholarly journals Dose dependent role of Emodin and BTB14431 in suspension colon cancer model in rats

2014 ◽  
Author(s):  
Stephan Rogalla ◽  
Jana Pohlenz ◽  
Vanessa Garcia ◽  
Gerold Koplin ◽  
Kirsten Fuehrer ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
In Silico ◽  
Total Mortality ◽  
Blood Analysis ◽  
Medical Plants ◽  
Potential Inhibitors ◽  
Tumor Drugs

Background. An “In Silico 2D/3D Conformer Screening” for structural similar antitumor substances to Curcumin was carried out and the novel antrachinone BTB14431 was found. Emodin, contained in several Chinese medical plants and BTB14431 are known to be potential inhibitors of the COP9-signalosome - stabilizing the tumor suppressor protein p53. The aim of this study was to analyze the suppressing effects on colorectal cancer in a standardized rat model (WAG/Rij). Methods. A suspension of CC531 colon cancer cells was applied to the cecum after laparotomy and, additionally, at the back of animals. Therapy was conducted twice daily for 7 days, with increasing doses of BTB14431, Emodin and with isotone sodium chloride solution (control) intravenously (iv) or intraperitoneally (ip). Therapy was initiated the day of tumor cell application. Peripheral blood samples were taken before surgery and on day 7. 21 days after the end of therapy, the animals were euthanized and tumor growth was evaluated. Results. Data showed a downward trend of the total tumor growth after iv and ip treatment with low doses of BTB14431 and Emodin. Differential blood analysis showed apoptosis, but no major changes in hemogram. Increasing doses of Emodin elevated total mortality rate exponentially. Conclusions.Although apoptosis was verified, no significant tumor suppressing effects could be observed for iv and ip treatment of both agents in our model. This stays in contrast to former in vitro studies. Agents remain viable novel substances. They will be the subject of upcoming studies. Additional data is needed to evaluate the significance of the “In Silico Screening” to identify potential in vivo anti-tumor drugs.

scholarly journals Dose dependent role of Emodin and BTB14431 in suspension colon cancer model in rats

2014 ◽  
Author(s):  
Stephan Rogalla ◽  
Jana Pohlenz ◽  
Vanessa Garcia ◽  
Gerold Koplin ◽  
Kirsten Fuehrer ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
In Silico ◽  
Total Mortality ◽  
Blood Analysis ◽  
Medical Plants ◽  
Potential Inhibitors ◽  
Tumor Drugs

Background. An “In Silico 2D/3D Conformer Screening” for structural similar antitumor substances to Curcumin was carried out and the novel antrachinone BTB14431 was found. Emodin, contained in several Chinese medical plants and BTB14431 are known to be potential inhibitors of the COP9-signalosome - stabilizing the tumor suppressor protein p53. The aim of this study was to analyze the suppressing effects on colorectal cancer in a standardized rat model (WAG/Rij). Methods. A suspension of CC531 colon cancer cells was applied to the cecum after laparotomy and, additionally, at the back of animals. Therapy was conducted twice daily for 7 days, with increasing doses of BTB14431, Emodin and with isotone sodium chloride solution (control) intravenously (iv) or intraperitoneally (ip). Therapy was initiated the day of tumor cell application. Peripheral blood samples were taken before surgery and on day 7. 21 days after the end of therapy, the animals were euthanized and tumor growth was evaluated. Results. Data showed a downward trend of the total tumor growth after iv and ip treatment with low doses of BTB14431 and Emodin. Differential blood analysis showed apoptosis, but no major changes in hemogram. Increasing doses of Emodin elevated total mortality rate exponentially. Conclusions.Although apoptosis was verified, no significant tumor suppressing effects could be observed for iv and ip treatment of both agents in our model. This stays in contrast to former in vitro studies. Agents remain viable novel substances. They will be the subject of upcoming studies. Additional data is needed to evaluate the significance of the “In Silico Screening” to identify potential in vivo anti-tumor drugs.

scholarly journals Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 75
Author(s):  
Yaru Peng ◽  
Zeneng Cheng ◽  
Feifan Xie
Keyword(s):  
Drug Interactions ◽  
In Silico ◽  
Drug Efficacy ◽  
Primary Concern ◽  
Factors Affecting ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Pharmacokinetic Drug

Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

The Inhibition Effect of Caveolin-1 on PANC1 Human Pancreatic Tumor Growth In vitro and In vivo*

2012 ◽  
Vol 38 (12) ◽  
pp. 1121-1131
Author(s):  
Xiao-Hui WANG ◽  
Ya-Min ZHENG ◽  
Ye-Qing CUI ◽  
Shuang LIU ◽  
Hai-Chen SUN ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Pancreatic Tumor ◽  
Caveolin 1 ◽  
Inhibition Effect

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

2018 ◽  
Vol 21 (3) ◽  
pp. 215-221
Author(s):  
Haroon Khan ◽  
Muhammad Zafar ◽  
Helena Den-Haan ◽  
Horacio Perez-Sanchez ◽  
Mohammad Amjad Kamal
Keyword(s):  
In Silico ◽  
Docking Studies ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Chronic Obstructive ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Inhibition ◽  
In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

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