A multi-objective multi-drug model for cancer chemotherapy treatment planning: A cost-effective approach to designing clinical trials

Bazrafshan, Nazila; Lotfi, Mohammad Mehdi

doi:10.1016/j.compchemeng.2015.12.004

Cited by 13 publications

(2 citation statements)

References 20 publications

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“…Ideas for treating cancer using multiple agents to target multiple molecules/pathways, for overcoming resistance and turning cancer into a manageable disease are being considered. Several plant-derived products provide an economical way to target multiple cancer molecules/pathways simultaneously [45,46] to complement and enhance effectiveness of currently available treatment regimens. Flavonoids and alkaloids in plant extracts have been used to overcome drug resistance [47].…”

Section: Discussionmentioning

confidence: 99%

Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets

De¹,

De²,

Sharma³

et al. 2020

J. Cancer

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Background: Ovarian cancer (OC), the most lethal gynecologic malignancy, is highly resistant to current treatment strategies. High-grade serous epithelial ovarian cancer (HGSOC) cells with increased somatic mutations and genomic instability and the resulting heterogeneous mutant phenotypes are highly resistant to therapy. Plant-derived natural products, including Amla (Emblica officinalis) extract (AE), have demonstrated potent anti-neoplastic properties. Recently we demonstrated that AE inhibits cell growth and the expression of angiogenic factors in OVCAR3 and SKOV3 OC cells in vitro as well as in xenografts in vivo. The goal of this study was to determine the anti-proliferative, anti-angiogenic and anti-metastatic effects of AE on carboplatinum-and taxol-resistant HGSOC cells carrying p53, BRCA1/2 mutations. Methods: Anti-proliferative and anti-metastatic effects of AE on recently characterized carboplatinum-and taxol-resistant HGSOC cells (TOV3041G, OV866(2), OV4453 and, OV4485) was determined using the MTT, migration, invasion and spheroid assays in vitro. To understand the mechanism of AE-induced changes in angiogenesis-related hypoxia-inducible factor 1α (HIF-1α) and insulin growth factor receptor 1 (IGF1R), and EMT-associated SNAIL1 and E-cadherin proteins were studied using immunostaining and Western blotting. In vivo effects of AE were determined using mouse xenograft tumor model of OC developed by subcutaneous injection of OV4485 cells that carry mutant p53 and BRCA1, most aggressive and resistant among HGSOC cell lines used in this study. Tumor growth was measured using morphometry. Immunostaining and Western blotting were used to determine changes in Ki67 (proliferation marker), CD31 (angiogenesis marker) as well as changes in HIF-1α, IGF1R, SNAIL1 and E-cadherin proteins. Results: AE significantly attenuated migration and invasiveness properties of all tested HGSOC cell phenotypes (P≤0.001), significantly reduced the expression of HIF-1α, IGF1R, and SNAIL1 and increased the expression of E-cadherin in all tested HGSOC cell lines (P=<0.05). Oral administration of AE for 4 weeks caused a significant regression of mouse xenograft tumor (>60%) that derived from OV4855 cells and decreased the expression of endothelial cell antigen-CD31, HIF-1α, IGF1R and SNAIL1 and increased the expression of E-cadherin in tumor tissues. Conclusions: AE sensitizes platinum-and taxol-resistant heterogenous HGSOC cells carrying mutations in p53, BRCA1/2 genes, and attenuates their malignant characteristics through targeting key signaling mechanisms of angiogenesis and metastasis. AE is a potential adjunct therapeutic agent for treating resistant, mutant, heterogenous OC.

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Section: Discussionmentioning

confidence: 99%

Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets

De¹,

De²,

Sharma³

et al. 2020

J. Cancer

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“…Cancer is a worldwide disease that is one of the leading causes of death [1]. In 2012 there was reported an estimate of 14.1 million adults diagnosed with cancer around the world and 8.2 million of deaths from this condition in the same year [2].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effect of Methanol Extracts and Partitions of Two Mexican Desert Plants against the Murine Lymphoma L5178Y-R

Quintanilla-Licea¹,

Gómez-Flores²,

Samaniego-Escamilla³

et al. 2016

AJPS

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Pachycereus marginatus (DC.) Britton & Rose and Ibervillea sonorae (S. Watson) Greene have been used in the Mexican traditional medicine for the treatment of various diseases, including cancer. The present study aims to investigate the cytotoxic activity of these plants against a murine lymphoma. Soxhlet extraction of dried and powdered plant material was performed with methanol. Also, a further partitioning of these methanolic extracts with hexane and ethyl acetate was achieved. The in vitro cytotoxic activity against the murine lymphoma L5178Y-R cell line was assessed via the colorimetric MTT assay. The methanol extract from P. marginatus exhibited high cytotoxic activity (up to 94%) at concentrations ranging from 3.9 to 500 µg/mL; however, hexane and ethyl acetate partitions from this methanolic extract showed lower but significant (p < 0.05) concentration-dependent cytotoxicity (hexane partition up to 94% at 500 µg/mL; ethyl acetate partition up to 94% at 65.5 µg/mL). The methanolic extract and partitions derived from I. sonorae also showed significant (p < 0.05) and concentration-dependent cytotoxicity against L5178Y-R cells at concentrations ranging from 7.81 to 500 µg/mL (methanolic extract up to 63% at 500 µg/mL; hexane partition up to 76% at 250 µg/mL; ethyl acetate partition up to 73% at 500 µg/mL). These results demonstrate that the methanol extracts and partitions from P. marginatus and I. sonorae possess significant cytotoxic activity against the murine lymphoma L5178Y-R and validate the ethnobotanical use of these plants for the treatment of diseases consistent with cancer symptomatology. Previous scientific reports describe the isolation of isoquinoline alkaloids of P. margi-* Corresponding author. R. Quintanilla-Licea et al. 1522natus as well as cucurbitacins from I. sonorae, phytochemicals that could be responsible for their observed cytotoxic activity in this research. The direct extraction with methanol of medicinal plants allows extracting of both high and low-polarity compounds, contrary to the simple extraction with water that only allows obtaining compounds of high polarity. The subsequent partition of the methanol extract with a solvent of low polarity (hexane) and another of medium polarity (ethyl acetate) allows making a preliminary fractionation of the bioactive molecules present in the plant that will facilitate the bioguided chromatographic isolation of the pure compounds responsible for the biological activity of the plant.

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Simulation analysis for tumor radiotherapy based on three‐component mathematical models

Hong

Zhang

2019

J Applied Clin Med Phys

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Objective To setup a three‐component tumor growth mathematical model and discuss its basic application in tumor fractional radiotherapy with computer simulation. Method First, our three‐component tumor growth model extended from the classical Gompertz tumor model was formulated and applied to a fractional radiotherapy with a series of proper parameters. With the computer simulation of our model, the impact of some parameters such as fractional dose, amount of quiescent tumor cells, and α/β value to the effect of radiotherapy was also analyzed, respectively. Results With several optimal technologies, the model could run stably and output a series of convergent results. The simulation results showed that the fractional radiotherapy dose could impact the effect of radiotherapy significantly, while the amount of quiescent tumor cells and α/β value did that to a certain extent. Conclusions Supported with some proper parameters, our model can simulate and analyze the tumor radiotherapy program as well as give some theoretical instruction to radiotherapy personalized optimization.

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A multi-objective multi-drug model for cancer chemotherapy treatment planning: A cost-effective approach to designing clinical trials

Cited by 13 publications

References 20 publications

Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets

Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets

Cytotoxic Effect of Methanol Extracts and Partitions of Two Mexican Desert Plants against the Murine Lymphoma L5178Y-R

Simulation analysis for tumor radiotherapy based on three‐component mathematical models

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