Synergistic effects of ultrasound-targeted microbubble destruction and TAT peptide on gene transfection: An experimental study in vitro and in vivo

Background: Arnica montana, containing helenalin as its principal active constituent, is the most widely used plant to treat various ailments. Recent studies indicate that Arnica and helenalin provide significant health benefits, including anti-inflammatory, neuroprotective, antioxidant, cholesterol-lowering, immunomodulatory, and most important, anti-cancer properties. Objective: The objective of the present study is to overview the recent patents of Arnica and its principal constituent helenalin, including new methods of isolation, and their use in the prevention of cancer and other ailments. Methods: Current prose and patents emphasizing the anti-cancer potential of helenalin and Arnica, incorporated as anti-inflammary agents in anti-cancer preparations, have been identified and reviewed with particular emphasis on their scientific impact and novelty. Results: Helenalin has shown its anti-cancer potential to treat multiple types of tumors, both in vitro and in vivo. It has also portrayed synergistic effects when given in combination with other anti- cancer drugs or natural compounds. New purification/isolation techniques are also developing with novel helenalin formulations and its synthetic derivatives have been developed to increase its solubility and bioavailability. Conclusion: The promising anti-cancer potential of helenalin in various preclinical studies may open new avenues for therapeutic interventions in different tumors. Thus clinical trials validating its tumor suppressing and chemopreventive activities, particularly in conjunction with standard therapies, are immediately required.

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Non-Viral Vectors for Gene Delivery

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681208666180110154233 ◽

2018 ◽

Vol 9 (1) ◽

pp. 4-11 ◽

Cited By ~ 5

Author(s):

Aparna Bansal ◽

Himanshu

Keyword(s):

Gene Therapy ◽

Viral Vectors ◽

Transfection Efficiency ◽

Gene Transfection ◽

Expression System ◽

Target Cells ◽

Specific Expression ◽

Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

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DDRE-07. DIPG HARBOUR ALTERATIONS TARGETABLE BY MEK INHIBITORS, WITH ACQUIRED RESISTANCE MECHANISMS OVERCOME BY COMBINATORIAL INHIBITION

Neuro-Oncology ◽

10.1093/neuonc/noaa215.252 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii62-ii62

Author(s):

Elisa Izquierdo ◽

Diana Carvalho ◽

Alan Mackay ◽

Sara Temelso ◽

Jessica K R Boult ◽

...

Keyword(s):

Drug Exposure ◽

Mapk Pathway ◽

Synergistic Effects ◽

Acquired Resistance ◽

Mek Inhibitor ◽

Resistance Mechanisms ◽

Genetic Alterations ◽

Mesenchymal Transition

Abstract The survival of children with diffuse intrinsic pontine glioma (DIPG) remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial, we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib (GI50 16-50nM) in samples, which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAF_G469V mutation, and those affecting PIK3R1 and NF1. However, treatment of PDX models and of a patient with trametinib at relapse failed to elicit a significant response. We generated trametinib-resistant clones (62-188-fold, GI50 2.4–5.2µM) in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, and expression signatures overlapping with inherently trametinib-insensitive primary patient-derived cells that predicted an observed sensitivity to dasatinib. Combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed highly synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.

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Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽

10.3390/molecules26082204 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2204

Author(s):

Meng-Die Yang ◽

Yang Sun ◽

Wen-Jun Zhou ◽

Xiao-Zheng Xie ◽

Qian-Mei Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Cell Viability ◽

Synergistic Effects ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

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Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892814666190116111827 ◽

2019 ◽

Vol 14 (1) ◽

pp. 5-18 ◽

Cited By ~ 8

Author(s):

Fabrizio Fontana ◽

Michela Raimondi ◽

Monica Marzagalli ◽

Roberta M. Moretti ◽

Marina Montagnani Marelli ◽

...

Keyword(s):

Cancer Prevention ◽

State Of The Art ◽

Synergistic Effects ◽

The State ◽

Therapeutic Interventions ◽

Multiple Tumor ◽

Anti Cancer ◽

Important Health

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.Objective:The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.Methods:Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.Results:TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.Conclusion:The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.

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