1,720,976 research outputs found
Three dimensional spheroids and gold nanoparticles in combined cancer therapy
Full text linkOne of the major issues in cancer radiotherapy (RT) is normal tissue toxicity.
Introduction of radiosensitizers like gold nanoparticles (GNPs) into cancer cells to
enhance the local RT dose is a promising technique that is being explored. However,
a large portion of experimentation involving GNPs has been done in simple two-dimensional (2D) monolayer models that cannot properly encapsulate the complex
heterogeneous interactions that occur in vivo. By introducing an in vitro three-dimensional (3D) model that better mimics the tumour microenvironment (TME),
we can more rapidly facilitate a quicker translation of various treatment technologies
like GNPs to the clinic. Further, clinical trials show that the chemotherapy drug
docetaxel (DTX) given in conjunction with RT can improve survival in high-risk
cancers. Addition of GNPs to this current DTX/RT protocol is expected to further
improve therapeutic benefits. Elucidation of a combined therapy of GNPs, DTX, and
RT to optimize treatment can better improve patient outcome and reduce normal
tissue toxicity by specifically targeting tumours and is completely novel research.
The work in this dissertation explores the application of GNPs to various elements
that are present in a TME. Many cell types are present in TME and contribute in
different ways to the proliferation of cancer. One of these cell lines, cancer associated
fibroblasts (CAFs), which can promote tumour growth and metastasis, was compared
to cancer epithelial cells and normal fibroblasts (FBs). Hence, we used FBs and CAFs
to evaluate the differences in GNP uptake and resulting radiation induced damage.
It was found that the CAFs had a much larger uptake of GNPs relative to the other
cells, with on average 265% more GNPs relative to cervical cancer cells while FBs
had only 7.55% the uptake of the tumour cells and 2.87% the uptake of CAFs. This
translated to increases in 53BP1-related DNA damage foci in CAFs (13.5%) and
tumour cells (9.8%) along with FBs (8.8%), compared to control with RT treatment.
This difference in DNA damage due to selective targeting of cancer associated cells
over normal cells may allow GNPs to be an effective tool in future cancer RT to battle
normal tissue toxicity while improving local RT dose to the tumour.
To expedite a quicker clinical translation, 3D tumor spheroid models were optimized and compared to 2D monolayer. The uptake of various sizes of GNPs was
tested on monolayer and spheroids to evaluate the differences between a 2D and 3D
model in similar conditions. Moreover, combined treatment of GNPs with DTX was
introduced and how they effect the uptake of the GNPs was elucidated.iv
In the 2D monolayer model, the addition of DTX induced a small increase of
uptake of GNPs of between 13% and 24%, while in the 3D spheroid model, DTX
increased uptake by between 47% and 186%. It was observed that the more complex
spheroid, which introduces an extracellular matrix, had larger uptake and penetration
of smaller GNPs (15 nm) relative to larger GNPs (50 nm). Moreover, while the
addition of DTX had a beneficial effect on the uptake of GNPs into cells, it also
synchronized the cells into a radiosensitive cell cycle phase. This translated to a larger
effect when radiation was introduced, in a combined treatment modality with GNP,
DTX, and RT. In spheroids, the addition of GNPs to the treatment regime decreased
the surviving tumour cells by 16-32% compared to samples not treated with GNPs.
Further, the addition of DTX seems to synergistically increase damage in some cancer
cell lines. This work highlights the necessity to optimize GNP treatment conditions in
a more realistic tumor-like environment. A 3D spheroid model can capture important
details which are absent from a simple 2D monolayer model.Graduat
Advances in Gold Nanoparticle-Based Combined Cancer Therapy
Full text linkAccording to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxicity. Among other inorganic NP systems, gold nanoparticle (GNP) based systems offer the means to further improve chemotherapy through controlled delivery of chemotherapeutics, while local radiotherapy dose can be enhanced by targeting the GNPs to the tumor. There have been over 20 nanotechnology-based therapeutic products approved for clinical use in the past two decades. Hence, the goal of this review is to understand what we have achieved so far and what else we can do to accelerate clinical use of GNP-based therapeutic platforms to minimize normal tissue toxicity while increasing the efficacy of the treatment. Nanomedicine will revolutionize future cancer treatment options and our ultimate goal should be to develop treatments that have minimum side effects, for improving the quality of life of all cancer patients.The authors would like to acknowledge Canada Foundation for Innovation (CFI), the British
Columbia government, Natural Sciences and Engineering Research Council of Canada (NSERC), British Columbia
Cancer, Vancouver Island (BCC), Centre for Advanced Materials and Related Technologies (CAMTEC),
and University of Victoria for their financial support.FacultyReviewe
Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics
Full text linkThe field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research
Optimized bio-nano interface using peptide modified colloidal gold nanoparticles
No full textAbstractThe interactions of synthetically produced colloidal gold nanoparticles (GNPs) with living organisms are gaining much attention in the biomedical sciences. While non-viral carriers, such as GNPs, are safer and more cost-efficient as compared to viral vectors, the probability of cell internalization is lower. In this paper, we discussed a method to increase cell internalization of GNPs using a specific peptide known as “RME-Peptide”. Our results showed an enhancement in cell uptake of peptide-capped GNPs. Furthermore, we investigated the exocytosis process of peptide-capped GNPs. Our results showed that the peptide-modified GNPs had a lower number of NPs exocytosed as compared to citrate-capped or as-made colloidal GNPs. Our study shows that bio-nano interface can be improved using specially designed peptides on colloidal GNPs. The outcome of this research will be beneficial for their applications in therapeutics and imaging
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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