1,721,020 research outputs found
What is the role of nanotechnology in diagnosis and treatment of metastatic breast cancer? Promising scenarios for the near future
Full text linkMetastatic breast cancer represents a diagnostic and therapeutic challenge due to tumor heterogeneity and to various physiological barriers that hinder drug delivery to the metastatic sites. To overcome these limitations, nanoformulated drugs have been developed and tested in preclinical studies, and few of them have been successfully translated into clinical practice. In particular, liposomal anthracyclines and nanoformulated albumin-bound paclitaxel have revealed an improved therapeutic index when compared to conventional chemotherapy, with significant reduction of drugs toxicity. Several strategies for nanoparticles engineering have more recently been explored to increase selectivity for tumor cells and to reach poorly accessible metastatic districts. Targeted nanoparticles, directed toward tumor markers and tissue-specific metastases, may provide effective devices in case of lowvascularized and small-sized metastases, thus paving the way for a real change in the natural history of metastatic disease. A number of targets have been identified and exploited for surface functionalization of different types of nanoparticles, which are currently undergoing preclinical studies. The aim of this review is to provide an overview of current nanotechnology applied to metastatic breast cancer diagnosis and treatment. Promising results encourage an upcoming translation of this research into clinical practice for an effective management of the disease in the near future
Progress in nonviral gene therapy for breast cancer and what comes next?
No full textIntroduction: The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation. Furthermore, they highlight innovative therapeutic strategies and the application of gene therapy in clinical trials for breast cancer. Expert opinion: Gene therapy has the potential to impact breast cancer research. Further efforts are required to increase the clinical application of RNAi-based therapeutics, especially in combination with conventional treatments. Innovative strategies, including genome editing and stem cell-based systems, may contribute to translate gene therapy into clinical practice. Immune-based approaches have emerged as an attractive therapeutic opportunity for selected breast cancer patients. However, several challenges need to be addressed before considering gene therapy as an actual option for the treatment of breast cancer
Ferritin nanocages : A biological platform for drug delivery, imaging and theranostics in cancer
Full text linkNowadays cancer represents a prominent challenge in clinics. Main achievements in cancer management would be the development of highly accurate and specific diagnostic tools for early detection of cancer onset, and the generation of smart drug delivery systems for targeted chemotherapy release in cancer cells. In this context, protein-based nanocages hold a tremendous potential as devices for theranostics purposes. In particular, ferritin has emerged as an excellent and promising protein-based nanocage thanks to its unique architecture, surface properties and high biocompatibility. By exploiting natural recognition of the Transferrin Receptor 1, which is overexpressed on tumor cells, ferritin nanocages may ensure a proper drug delivery and release. Moreover, researchers have applied surface functionalities on ferritin cages for further providing active tumor targeting. Encapsulation strategies of non metal-containing drugs within ferritin cages have been explored and successfully performed with encouraging results. Various preclinical studies have demonstrated that nanoformulation within ferritin nanocages significantly improved targeted therapy and accurate imaging of cancer cells. Aims of this review are to describe structure and functions of ferritin nanocages, and to provide an overview about the nanotechnological approaches implemented for applying them to cancer diagnosis and treatment
One-step nucleic acid amplification (OSNA) fits better with lower cost in breast cancer axillary management
Full text linkIntroduction: One-Step Nucleic Acid Amplification (OSNA) has been already validated for Analysis of Sentinel Node (SLN) in breast cancer. We investigated benefits of OSNA beyond accuracy, with a focus on cost-effectiveness.
Methods: 253 consecutive breast cancer patients were reviewed: SLN was analyzed by OSNA in 114 cases and by standard
histopathology in 139 cases. Nodal involvement detection, reintervention rate, time between surgery and adjuvant therapy were assessed. A cost analysis of OSNA vs. standard histopathology was performed.
Results: With OSNA the re-intervention rate significantly decreased (10.79% vs. 0%, p = 0.0003), and adjuvant therapy started earlier (38.5 days vs. 23.8 days, p < 0.0001). Total cost per patient was 5,990.8€ for histopathology vs. 4,308€ with OSNA (p < 0.0001) if positive SLN. In case of negative SLN costs were similar (2,419.6€ vs. 2,425.2€, p = 0.947).
Conclusions: OSNA reduces re-interventions, allows to start earlier adjuvant therapy and is more cost-effective than histopathology
H-ferritin allows nanometronomic treatment of breast cancer with doxorubicin preventing drug resistance and circumventing cardiotoxicity
Full text linkAbstract
Chemotherapeutic treatment of breast cancer is based on maximum tolerated dose (MTD) approach.1 However, advanced stage tumors are not effectively eradicated by MTD owing to suboptimal drug targeting, onset of therapeutic resistance and neoangiogenesis. In contrast, “metronomic” chemotherapy is based on frequent drug administrationsat lower doses, resulting in neovascularization inhibition and induction of tumor dormancy.1,2 However, several limiting factors remain for LDM in order to displace MTD treatments in clinical practice, including 1) low drug accumulation at tumor site,2 2) controversial effectiveness against chemoresistance in advanced metastatic cancers, and 3) acquired resistance after prolonged treatment. Recent advances in nanotechnology could offer groundbreaking solutions to improve the effectiveness of LDM chemotherapy, by taking advantage of the unique targeting efficiency of engineered nanocarriers.3 Here, we propose a new concept of “nanometronomic” chemotherapy, exploiting the H-ferritin (HFn)-mediated targeted delivery of doxorubicin (DOX)in an aggressive and metastatic breast cancer mouse model with DOX-inducible chemoresistance. HFn nanocages naturally target cancer cells4 owing to its affinity for transferrin receptor 1. HFn-DOX was recently demonstrated to overcome chemoresistance by actively promoting DOX nuclear translocation in vitro5,6 and was tested as a MTD treatment on a DOX-sensitive tumor model with encouraging results.7 We find that LDM administration of HFn-DOX strongly improves the antitumor potential of DOX chemotherapy arresting the tumor progression. Indeed, in vitro and in vivo results demonstrate that HFn nanocages mediate the nuclear delivery of DOX and increase DOX accumulation both in tumor tissue and in cancer cell nuclei, resulting in increased efficacy. Moreover, we find that HFn-DOX antitumor effect is attributable to multiple nanodrug actions beyond cell killing, including inhibition of tumor angiogenesis and avoidance of chemoresistance. Otherwise, although an even better reduction of tumor progression was achieved with liposomal DOX (pl-DOX) a five-fold increase in MDR-1-positive cells has been displayed, suggesting that liposomal DOX is not suitable in view of a protracted metronomic treatment, due to the onset of chemoresistance. Multiparametric assessment of heart tissues, including histology, ultrastructural analysis of tissue morphology, and measurement of markers of reactive oxygen species and hepatic/renal conditions, provided evidence that metronomic HFn-DOX allowed us to overcome cardiotoxicity contrary to what is observed with DOX and pl-DOX. Our results suggest that HFn-DOX has tremendous potential for the development of “nanometronomic” chemotherapy toward safe and tailored oncological treatments.
1. Kareva I, et al. Cancer Lett 2015; 358: 100.
2. Kerbel RS. Cancer Res Treat 2007; 39: 150.
3. Cruz-Munoz W, et al. Angiogenesis 2014; 7: 661.
4. Corsi F, Mazzucchelli S. Ther Deliv. 2016; 7: 149.
5. Bellini M, et al.. J Controlled Rel 2014;196: 184.
6. Zhang L, et al. Adv. Healthcare Mat. 2015; 4: 1305.
7. Liang M, et al. Proc Natl Acad Sci USA 2014; 111: 14900.
Citation Format: Mazzucchelli S, Fiandra L, Bellini M, Truffi M, Rizzuto MA, Sorrentino L, Longhi E, Nebuloni M, Prosperi D, Corsi F. H-ferritin allows nanometronomic treatment of breast cancer with doxorubicin preventing drug resistance and circumventing cardiotoxicity [abstract]. In: Proceedings of the Thirty-Ninth Annual CTRC-AACR San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-12-17.</jats:p
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
In vitro permeation of FITC-loaded ferritins across a rat blood-brain barrier : A model to study the delivery of nanoformulated molecules
No full textBrain microvascular endothelial cells, supported by pericytes and astrocytes endfeet, are responsible for the low permeation of large hydrosoluble drugs through the blood-brain barrier (BBB), causing difficulties for effective pharmacological therapies. In recent years, different strategies for promoting brain targeting have aimed to improve drug delivery and activity at this site, including innovative nanosystems for drug delivery across the BBB. In this context, an in vitro approach based on a simplified cellular model of the BBB provides a useful tool to investigate the effect of nanoformulations on the trans-BBB permeation of molecules. This study describes the development of a double-layer BBB, consisting of co-cultured commercially available primary rat brain microvascular endothelial cells and astrocytes. A multiparametric approach for the validation of the model, based on the measurement of the transendothelial electrical resistance and the apparent permeability of a high molecular weight dextran, is also described. As proof of concept for the employment of this BBB model to study the effect of different nanoformulations on the translocation of fluorescent molecules across the barrier, we describe the use of fluorescein isothiocyanate (FITC), loaded into ferritin nanoparticles. The ability of ferritins to improve the trans-BBB permeation of FITC was demonstrated by flux measurements and confocal microscopy analyses. The results suggest this is a useful system for validating nanosystems for delivery of drugs across the BBB
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
- …
