Mathematical Modeling and Dynamics of Oncolytic Virotherapy

Mapping Intimacies ◽

10.5772/intechopen.96963 ◽

2021 ◽

Author(s):

Abdullah Abu-Rqayiq

Keyword(s):

Mathematical Modeling ◽

Fractional Derivative ◽

Cancer Treatment ◽

Cancer Cells ◽

Viral Infections ◽

Oncolytic Virotherapy ◽

Control Parameters ◽

Approaches To Studying ◽

Asymptotic Dynamics ◽

The Cost

Oncolytic virotherapy is a cancer treatment that uses competent replicating viruses to destroy cancer cells. This field progressed from earlier observations of accidental viral infections causing remission in many malignancies to virus drugs targeting and killing cancer cells. In this chapter, we study some basic models of the oncolytic virotherapy and their dynamics. We show how the dynamical system’s theory can capture the behavior of the solutions of those models and provide different approaches to studying the models. We study the thresholds that enable us to classify asymptotic dynamics of the solutions. Fractional-derivative approach tells us about the memory of the derivative and related solutions of the models. We also study the affect of introducing control parameters on the cost of the therapy.

Download Full-text

Mathematical modeling of radiotherapy cancer treatment using Caputo fractional derivative

Computer Methods and Programs in Biomedicine ◽

10.1016/j.cmpb.2019.105306 ◽

2020 ◽

Vol 188 ◽

pp. 105306 ◽

Cited By ~ 4

Author(s):

Musiliu Folarin Farayola ◽

Sharidan Shafie ◽

Fuaada Mohd Siam ◽

Ilyas Khan

Keyword(s):

Mathematical Modeling ◽

Fractional Derivative ◽

Cancer Treatment ◽

Caputo Fractional Derivative

Download Full-text

ABOUT NECESSITY OF MATHEMATICAL MODELING OF THE BUSINESS PROCESS OF COST ESTIMATE CALCULATIONS IN THE CONSTRUCTION OF OIL AND GAS FACILITIES

Oil and Gas Studies ◽

10.31660/0445-0108-2017-6-139-145 ◽

2017 ◽

pp. 139-145

Author(s):

R. I. Hamidullin ◽

L. B. Senkevich

Keyword(s):

Mathematical Modeling ◽

Quality Assessment ◽

Business Process ◽

Oil And Gas ◽

Oil And Gas Industry ◽

Gas Industry ◽

Construction Organizations ◽

The Cost ◽

Cost Of Construction

A study of the quality of the development of estimate documentation on the cost of construction at all stages of the implementation of large projects in the oil and gas industry is conducted. The main problems that arise in construction organizations are indicated. The analysis of the choice of the perfect methodology of mathematical modeling of the investigated business process for improving the activity of budget calculations, conducting quality assessment of estimates and criteria for automation of design estimates is performed.

Download Full-text

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

Current Cancer Drug Targets ◽

10.2174/1568009619666191019143539 ◽

2020 ◽

Vol 20 (2) ◽

pp. 130-145 ◽

Cited By ~ 9

Author(s):

Keywan Mortezaee ◽

Masoud Najafi ◽

Bagher Farhood ◽

Amirhossein Ahmadi ◽

Dheyauldeen Shabeeb ◽

...

Keyword(s):

Targeted Therapy ◽

Cancer Treatment ◽

Cancer Cells ◽

Clinical Studies ◽

Normal Tissue ◽

Medical Science ◽

Treatment Modalities ◽

Radiation Toxicity ◽

Normal Tissues ◽

Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

Download Full-text

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180313154724 ◽

2018 ◽

Vol 18 (8) ◽

pp. 1138-1147 ◽

Cited By ~ 1

Author(s):

Esra Metin ◽

Pelin Mutlu ◽

Ufuk Gündüz

Keyword(s):

Breast Cancer ◽

Polyethylene Glycol ◽

Magnetic Nanoparticles ◽

Cancer Treatment ◽

Cancer Cells ◽

Drug Loading ◽

Gravimetric Analysis ◽

Polyethylene Glycol 1000 ◽

Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

Download Full-text

Perspectives on the Therapeutic Benefits of Arginine Supplementation in Cancer Treatment

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190116121451 ◽

2019 ◽

Vol 19 (7) ◽

pp. 913-920

Author(s):

Fabiani L. R. Beal ◽

Pedro R. Beal ◽

Juliana R. Beal ◽

Natan Carvalho-Neves ◽

Octávio L. Franco ◽

...

Keyword(s):

Amino Acid ◽

Side Effects ◽

Cancer Treatment ◽

Treatment Strategies ◽

Endothelial Permeability ◽

The Elderly ◽

Therapeutic Benefits ◽

Cell Growth And Differentiation ◽

The Cost ◽

Arginine Supplementation

Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. Objective: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. Results: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. Conclusion: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.

Download Full-text

Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

Scientific Reports ◽

10.1038/s41598-021-94483-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amanda W. K. AuYeung ◽

Robert C. Mould ◽

Ashley A. Stegelmeier ◽

Jacob P. van Vloten ◽

Khalil Karimi ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Vesicular Stomatitis Virus ◽

Cell Response ◽

Viral Infections ◽

T Cell Response ◽

Oncolytic Viruses ◽

Oncolytic Virotherapy ◽

Cell Immunity ◽

Vesicular Stomatitis

AbstractVaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.

Download Full-text

Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells

Cancers ◽

10.3390/cancers13153790 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3790

Author(s):

Gro Elise Rødland ◽

Sissel Hauge ◽

Grete Hasvold ◽

Lilli T. E. Bay ◽

Tine T. H. Raabe ◽

...

Keyword(s):

Lung Cancer ◽

Cell Viability ◽

Cancer Treatment ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Combined Treatment ◽

Cancer Cell Lines ◽

Variable Extent ◽

Synergistic Induction

Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

Download Full-text

2D Nanomaterial, Ti3C2 MXene-Based Sensor to Guide Lung Cancer Therapy and Management

Biosensors ◽

10.3390/bios11020040 ◽

2021 ◽

Vol 11 (2) ◽

pp. 40

Author(s):

Mahek Sadiq ◽

Lizhi Pang ◽

Michael Johnson ◽

Venkatachalem Sathish ◽

Qifeng Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Treatment ◽

Cancer Cells ◽

Small Cell ◽

Gas Chromatography Mass Spectrometry ◽

High Signal ◽

Research Attention ◽

Lung Cancer Treatment ◽

Anti Cancer ◽

Cox 2

Major advances in cancer control can be greatly aided by early diagnosis and effective treatment in its pre-invasive state. Lung cancer (small cell and non-small cell) is a leading cause of cancer-related deaths among both men and women around the world. A lot of research attention has been directed toward diagnosing and treating lung cancer. A common method of lung cancer treatment is based on COX-2 (cyclooxygenase-2) inhibitors. This is because COX-2 is commonly overexpressed in lung cancer and also the abundance of its enzymatic product prostaglandin E2 (PGE2). Instead of using traditional COX-2 inhibitors to treat lung cancer, here, we introduce a new anti-cancer strategy recently developed for lung cancer treatment. It adopts more abundant omega-6 (ω-6) fatty acids such as dihomo-γ-linolenic acid (DGLA) in the daily diet and the commonly high levels of COX-2 expressed in lung cancer to promote the formation of 8-hydroxyoctanoic acid (8-HOA) through a new delta-5-desaturase (D5Di) inhibitor. The D5Di does not only limit the metabolic product, PGE2, but also promote the COX-2 catalyzed DGLA peroxidation to form 8-HOA, a novel anti-cancer free radical byproduct. Therefore, the measurement of the PGE2 and 8-HOA levels in cancer cells can be an effective method to treat lung cancer by providing in-time guidance. In this paper, we mainly report on a novel sensor, which is based on a newly developed functionalized nanomaterial, 2-dimensional nanosheets, or Ti3C2 MXene. The preliminary results have proven to sensitively, selectively, precisely, and effectively detect PGE2 and 8-HOA in A549 lung cancer cells. The capability of the sensor to detect trace level 8-HOA in A549 has been verified in comparison with the traditional gas chromatography–mass spectrometry (GC–MS) method. The sensing principle could be due to the unique structure and material property of Ti3C2 MXene: a multilayered structure and extremely large surface area, metallic conductivity, and ease and versatility in surface modification. All these make the Ti3C2 MXene-based sensor selectively adsorb 8-HOA molecules through effective charge transfer and lead to a measurable change in the conductivity of the material with a high signal-to-noise ratio and excellent sensitivity.

Download Full-text

716 Cell-based virotherapy for targeting cancers

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0716 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A758-A758

Author(s):

Duong Nguyen ◽

Alberto Gomez ◽

Forrest Neuharth ◽

Ashley Alamillo ◽

Thomas Herrmann ◽

...

Keyword(s):

Stem Cells ◽

Vaccinia Virus ◽

Cancer Cells ◽

Neutralizing Antibodies ◽

Immune Cell ◽

Human Cancer ◽

Oncolytic Viruses ◽

Oncolytic Virotherapy ◽

Adaptive Immune ◽

Immune Barriers

BackgroundOncolytic virotherapy has been recognized as a promising new therapy for cancer for decades but only few viruses have been approved worldwide. The therapeutic potential of oncolytic viruses can be severely restricted by innate and adaptive immune barriers making oncolytic virus clinically inefficient. To overcome this obstacle, we utilized adipose-derived stem cells (AD-MSC) loaded with tumor selective CAL1 oncolytic vaccinia virus to generate a new therapeutic agent called SNV1 (SuperNova-1).MethodsCAL1 vaccinia virus was tested for its ability to replicate and selectively kill various human cancer cell lines in vitro and in vivo. Additionally, CAL1 was loaded into adipose-derived mesenchymal stem cells to generate SuperNova1 (SNV1). Both CAL1 and SNV1 were tested for their ability to kill cancer cells in the presence of active complement and neutralizing antibodies in cell culture as well as in mice. Immune cell infiltration of the treated and untreated tumors was analyzed by flow cytometry.ResultsCAL1 showed preferential amplification and killed various tested human (PC3, FaDu, MDA-MB-231, RPMI) and mouse cancer cells (CT26, EMT6, TRAMP-C2, RM1). In animals, CAL1 caused tumor regression in PC3 and CT26 mouse models without signs of toxicity. SNV1 significantly enhanced protection of CAL1 virus from clearance by the immune system as compared to naked CAL1 virus, leading to higher therapeutic efficacy in animals. Five days after SNV1 administration, tumor infiltrating lymphocytes (TILs) from both treated and untreated tumors showed increased CD4 and CD8 T-cell infiltrations. Importantly, we documented a decreased frequency of Tregs, and improved effector to Treg ratios, which was associated with inhibition of tumor growth at the treated tumor site and also at distant untreated sites.ConclusionsCAL1 is potentially used as an oncolytic agent. In addition, SNV1 cell-based platform protects and potentiates oncolytic vaccinia virus by circumventing humoral innate and adaptive immune barriers, resulting in enhanced oncolytic virotherapy. Particularly, SNV1 provided instantly active viral particles for immediate infection and simultaneous release of therapeutic proteins in the injected tumors.

Download Full-text