3^rd International Conference on Integrative Biology August 04-06, 2015 Valencia, Spain

Mourad Aboul-Soud received his Ph.D. from the University of Edinburgh, Scotland UK and completed 3-year postdoctoral studies at the University of Nottingham (England UK) and INRA (Bordeaux-France). He is a full professor of Biochemistry & Molecular Biology at both Cairo (Egypt) and King Saud Universities (Riyadh-KSA). Prof. Aboul-Soud's main area of research isprimarily focused in the fields of biochemistry, molecular biology and genetic engineering.

This study aims at employing recent genetic engineering tools to control the expression level of selected JAZ genes, a new family of repressors of jasmonate(JA) signaling, in tomato in order to generate salt-tolerant tomato plants able to grow under limited water availability and saline soil conditions, typical of some regions of the Kingdom of Saudi Arabia (KSA). Wehave successfully dissected the entire family oftomato JAZ-repressor genes (SlJAZ) involved in drought and salinity tolerance via phylogenetic analyses. Four SlJAZs were identified with potential role in abiotic stress tolerance of which only two (SlJAZ2 and SlJAZ3) were targeted for in planta transgenic analysis and mis-expression studies to elucidate their functional roles. Atransgenic approach was employed to silence (Haiprin) the SlJAZ3 gene in tomato miniature Micro-Tom plants. For this, a gene-specific 400-nt sequence was used for the RNA interference (RNAi) silencing approachThe Gateway® LR Clonase® system was utilized to facilitate the cloning ofthe silencing(hairpin) destination vector. The resulting expression clonetransformed into tomato via an Agrobacterium-mediated cotyledon-transformation strategy. A hydroponically-grown system was established to conduct a full transcriptional profiling of the entire SIJAZ gene family (12 members) in different tissues (leaves, roots, floral organs and fruits) of wild-type Micro-Tom tomato plants. This has been achievedviaa real-time quantitative PCR (qRT-PCR) strategy in response to abiotic stresses. Initial expression profiling of all members of the JAZ genes in tomato indicated differential expression in response to abiotic stresses such as salinity, jasmonic acid and abscisic acid. Yeast-Two Hybrid (Y2H) studies, where both the SlJAZ2 and SlJAZ3had been used as prey (pGAD vector) and COI.1 as bait (pGBK vector), revealed that SlJAZ2, but not SlJAZ3, directly interacts with SlCOI1. Subsequently, a targeted large-scale Chemical Genomic Screen has been conducted to identify molecules inducing the SlJAZ2/SlCOI1 interaction, therefore acting as “molecular glue” for the JA-Ile co-receptor complex. The screen is currently underway using a state-of-the-art natural product library (NPL-720) representinga collection of 720 pure individual compounds primarily from plant and also from bacteria, fungi, and animal sources. This approach will open up new horizons of increasing tomato productivity in KSAunder harsh environmental conditions such as drought and salinity. It will also help the development of plant molecular biology and biotechnology platforms for transgenic crops with superior agricultural traits.

Francisco Torrens has completed his PhD at the age of 29 years from Universitat de València and postdoctoral studies from Université de Nancy I. He is the director of the Molecular Simulation and Computer-Aided Drug Design and Development Unit in the Institute for Molecular Science UV, a premier nonprofit university. He has published more than 350 papers in reputed journals, 1600 presentations and has been serving as an editorial board member of repute.

Mentha pulegium and Eucalyptus camaldulensis are important plant species with applications in flavouring processed foods. Their essential oils were tested for antifungal activity to explore biocontrol ways vs. fungal rot of apples in storage. Extracts analyses by gas chromatography–mass spectrometry revealed M. pulegium dominated by pulegone and E. camaldulensis, by 1,8 cineole and alpha-pinene. Oils antifungal activity was studied vs. Alternaria alternata and Penicillium expansum. Oil of M. pulegium is thrice more active than E. camaldulensis. Chemical components show synergism. Inhibition suggests food-preservation application. Classification algorithms are proposed based on information entropy and its production. Oils components are classified by numbers of C=C bonds, O atoms and cycles. Classification algorithms are based on information entropy. When applying procedures to moderate-size sets, excessive results appear compatible with data and suffer combinatorial explosion; however, after equipartition conjecture one obtains selection criterion resulting from classification between hierarchical trees. Information entropy permits classifying oils components and agrees with principal component analyses. Periodic table of oils constituents shows that those in the same group present similar properties; components also in the same period, maximum resemblance. Table is extended to other oils and anti inflammatory drugs.

A master's degree in Operative Techniques and Experimental Surgery for the Federal University of São Paulo ( 1999) and PhD for the Federal University of São Paulo (2001 ). Currently is an Associate professor of the Faculty of Medicine of the Federal University of Mato Grosso do Sul. She has experience in Medicine , with emphasis in Surgery . Guidance teacher in the Postgraduate Course in Health Sciences UFMS. Line of Research in Stem Cells. Coordinator of CeTroGen ( Center for Studies in Stem Cells , Tissue Engineering and Genetic Toxicology ).

The use of mesenchymal stem cells (MSCs) in experimental, clinical, and therapeutic trials has grown in recent years. However, the issue remains of whether these procedures are completely safe for transplant patients. Therefore, this study was designed and carried out with the aim of evaluating two different comet assay protocols for genomic damage pattern analysis in MSCs derived from adipose tissue. The analyzed and interpreted results suggest that genetic testing is needed to support clonal expansion safety in cell therapy procedures with MSCs. Furthermore, they also suggest that if the comet assay technique would be used as a genomic integrity screening assay, the protocol performed at pH = 12 (that yielded a frequency of damaged cells: tail intensity = 9.50 ± 0.60, tail moment = 0.0122 ± 0.0007; results are reported as means ± standard deviation) would be indicated as genomic damage, and that subsequent single-strand breaks occur at pH > 13 (frequency of damaged cells: tail intensity = 30.71 ± 4.23, tail moment = 0.0447 ± 0.0073). Our study demonstrates that, in the era of regenerative medicine, it is necessary to standardize and establish a battery of tests in order to identify genomic damage prior to MSC transplantation.

Sílvia M. Rocha is assistant professor in the Chemistry Department at the Aveiro University. She is BA in Pharmaceutical Sciences at the Pharmacy Faculty (Coimbra University), and PhD in Chemistry (Aveiro University). For the last 22 years, she has performed studies on the characterization of plant-derived natural products, prospection of bioactive compounds, and metabolomics applied to human fluids, plants and microbial systems. Her main skills are oriented to sample preparation and high through-put analysis based on comprehensive two-dimensional gas chromatography and mass spectrometry developments. She published over 85 SCI papers, 2 books, 7 book chapters, and 3 patent applications.

Hospital-acquired infections are present worldwide, and microorganisms such as viruses, bacteria, fungi and parasites can be responsible for such infections. Fungal infections exhibit low occurrence; however, because they take longer to detect and treat, high rates of morbidity and mortality are known. Thus, fungal infections, namely those associated to Aspergillus niger, represent actual challenges, especially for elderly, neonates or those having an underlying disease or under immunosuppressive drug treatments. Microbial metabolomics has been breaking new ground as a very useful tool in several areas, including those related to microbial diagnosis. Microorganisms produce several volatile metabolites, the whole of which can be used as unique chemical fingerprints of each species, and possibly of strain. This richness of information holds the promise for diagnosing infections. This research study aims to in-depth study the A. niger exometabolome in order to establish metabolites pattern that can be further exploited for fungal diagnosis. A methodology based on advanced multidimensional gas chromatography (HS-SPME/GC×GC-ToFMS) tandem with multivariate analysis was developed. Different growth conditions were assayed. A. niger exometabolome revealed around 500 metabolites, distributed over several chemical families, being the major ones alcohols, aldehydes, esters, hydrocarbons, ketones and terpenoids. A subset of 44 metabolites, defined as the A. niger metabolomic biomarkers pattern, was selected and successfully used to distinguish this species from others previously chosen, revealing its useful potential. Acknowledgments: Funding is acknowledged from the FEDER through the COMPETE Programme and from the FCT, Portugal, under Research Units QOPNA (projects PEst-C/QUI/UI0062/2013 and PTDC/QUI-QUI/117803/2010) and CESAM (project Pest-C/MAR/LA0017/2013).

Aleya Ferdausi, Assistant Professor in the Department of Genetics and Plant Breeding, Bangladesh Agricultural University, completed her Masters degree from the same department of the same University. She has been awarded study leave and a Commonwealth Scholarship to pursue her PhD in the UK at the Institute of Integrative Biology, University of Liverpool.

The Amaryllidaceae alkaloids e.g. galanthamine, lycorine and narsiclasine are noted for their pharmaceutical properties. Galanthamine is a long acting, selective, reversible, and competitive acetylcholinesterase inhibitor approved for the treatment of early to mild stage Alzheimer’s diseases in the UK. It is currently obtained from plant material (especially Narcissus, Galanthus, Leucojum and Lycoris species, including collected from the wild) since total chemical synthesis is not economic. The UK is one of the major producers in the world of Narcissus, but cultivars have been selected for flower, rather than alkaloid production. The biosynthesis of alkaloids by plants using in vitro systems has been considered as tools for drug discovery and production. The biosynthetic pathways, especially for galanthamine, are starting to be understood, but are still far from complete. Two important steps towards the goal of improved yields from whole plant or cell culture systems are identification of genes and their alkaloid products and also developing culture systems for optimized alkaloid production. We are using a combination of transcriptomics for gene discovery within different daffodil cultivars and tissues towards this goal.

Maria-João Queiroz has completed her first degree in Pharmaceutical Sciences in the University of Porto-Portugal (1986), PhD in Organic Chemistry (1993) in the University of Minho- Portugal and carried out postdoctoral studies in the University of Metz-France (1994). She is Coordinator Researcher since June 2009 and she was the director of the Chemistry Research Centre of the University of Minho from January 2010 to March 2015. She has published more than 110 papers in reputed journals of Organic Chemistry and Medicinal Chemistry and attended to more than 150 conferences around the world. She was also the responsible of several financed projects in Medicinal Chemistry, coordinating different teams.

New fluorescent N-(2 and 3-methoxyphenyl)thieno[3,2-b]pyridin-7-amines were synthesized by C-N coupling of 7-bromothieno[3,2-b]pyridine with 2 or 3 methoxyanilines and gave very low growth inhibitory (GI50) values when studied in human tumor cell lines but also in non-tumor cells. So, pursuing a future clinical administration of these compounds, they were encapsulated in nanoliposomes, due to the toxicity presented in vitro in non-tumor cells. The compounds are reasonably fluorescent in solvents of different polarity, exhibiting fluorescence quantum yields between 10% and 60%. Nanoliposomes are technological developments for the encapsulation and delivery of bioactive agents. Because of their biocompatibility and biodegradability, along with their size, nanoliposomes have potential applications in a vast range of fields, including nanotherapy. Nanoliposomes are able to enhance the performance of bioactive agents by improving their bioavailability, in vitro and in vivo stability, as well as preventing their unwanted interactions with other molecules. These compounds have been successfully encapsulated in different nanoliposome formulations as revealed by fluorescence emission and fluorescence anisotropy measurements. These results are important for future drug delivery developments using these compounds as antitumor agents.

Maria Mirto is completing her master studies in Health Biology at University of Palermo (Italy). She worked and is working with a joint work group dedicated to Epigenetic studies in Acute Myeloid Leukemia consisting of Cellular biology and Genetics Lab of Department STEBICEF (University of Palermo) and Oncohematologic Integrated Diagnostic Lab (United Hospitals “Villa Sofia Cervello” Palermo) – Italy. These teams have several publications in topic. These presented results are part of her degree thesis.

Acute Myeloid Leukaemia (AML) is frequently associated to normal karyotype and DNMT3A mutations (R882). Since we previously demonstrated distinctive miRNA expression in some AML groups, we study 384 miRNA in 9 selected DNMT3A-mutated NK-AML patients. Comparing these data with our previous results obtained in 31 DNMT3A-unmutated AML, we focused on a significant up-regulation of miR-155, miR-29a, miR-196b and miR-25. We investigated expression of these miRNAs in additional 24 DNMT3A-mutated AML patients and we confirm the up-regulation of miR-155, miR-29a and miR-196b; in particular, we judged very interesting the over expression of miR-29a since is known to directly target DNMT3A, TET1 and TDG mRNAs. Evaluating the expression levels of these targets in 17 AML DNMT3A-mutated patients, we revealed a no significant differences in expression of DNMT3A and TDG but a significant down-regulation of TET1. These data suggest that miR-29a acts as DNA methylation-regulator: in presence of DNMT3A activating mutations and TET1 down-regulation it may probably cause a perturbation of DNA methylation. In fact, analyzing the methylation of the bone marrow genomic DNA from 3 DNMT3A-mutated and 3 DNMT3A-unmutated cases by Methylation Sensitive Arbitrarily Primed-PCR, we found a genomic hypermethylation of DNMT3A-mutated cells compared to the unmutated ones. How DNMT3A mutations contribute to leukemogenesis is not yet well characterized. Uncovering how DNMT3A mutations affect DNA methylation and epigenetic regulation of gene expression may have important implications in treatment selection because DNA hypomethylating agents are increasingly used in AML therapies, and response to these drugs may be affected by DNMT3A changed function.

Ayse SEN has completed herPhDfromIstanbul University (2011) and postdoctoral studies from FAO/IAEA Plant Breeding and Genetics Laboratory (PBGL) of FAO/IAEA Agriculture and Biotechnology Laboratories (2014) in Seibersdorf, Austria. Currently is a Research Assistant the Istanbul University. Dr. Sen’s main area of research tracks is in the field ofagricultural and biological science, particularly in Mutation Breeding, Molecular Plant Breeding, Abiotic Stress Factors (Drought, Salinity etc.), Oxidative Stress, Antioxidant Defense System, Magnetic Field, Radiobiology in plants.

Torelease of new mutants is a long process that may need up to 12 years to be completed for some crops.This process depends largely on the nature of propagation of the crop, the targeted trait and the ability to recognize and select individuals carrying these traits in segregating populations.Induced mutation techniques and combination with advanced techniques such as doubled haploids and somatic embryogenesis techniques provide alternativefor generating variability for biotic/abiotic stress resistance or tolerance and for manipulating and evaluating them in efficient ways for improved germplasm. These techniques also are important tools for modern crop improvement programs to increase breeding efficiency and shorten the time breeding programs. Although plant mutation breeding is faster than conventional breeding, application of these techniques speed up the time from mutation induction to mutant variety release. The present investigation was undertaken to study the somatic embryogenesis and doubled haploid techniques for improvement of wheat mutant to reach sufficient homozygosity to have advance a mutant line. This allowed us to choose the more apt of these two strategies for the next stage of research, combining plant tissue culture strategy via mutation breeding.

Jong-Chan Chae has completed his PhD from Chungbuk National University and postdoctoral studies from Rutgers University. He is vice dean of college of environmental &bioresource sciences, Chonbuk National University. He has been serving as an editorial board member of “Journal of Microbiology and Biotechnology”.

Aromatic hydrocarbons have attracted concernas a kind of environmental pollutants along with possible health threats.Comamonastestosteroni strain P19 was originally isolated as a biphenyl degrader and capable of degrading several aromatic compounds as a sole source of carbon and energy.Here, we describe the metabolic insight by genetic and physiological analysis indicating how aromatic compounds are metabolized in C. testosteroni strain P19. The strain has a circular chromosome of 5,633,218 bp with a G + C content of 67.65% and one plasmid. The annotation identified gene clusters encoding essential proteins for metabolizing several aromatic hydrocarbons, including anthranilate, benzoate, biphenyl, m-hydroxybenzoate, p-hydroxybenzoate, p-methoxybenzoate, phenol, phthalate, protocatechuate, terephthalate etc. Random plasposon mutagenesis confirmed that the predicted gene clusters were essential in the metabolic pathways of the compounds. In addition, we identified novel metabolite on degradation of ferulate, which had very similar structure to vanillate. Based on structural assignment, the unknown product was revealed as a dimer of vanillatethat was a novel intermediate in ferulate degradation pathway. Subsequently, genomic approach suggested the metabolic network of aromatic compounds in C. testosteroni strain P19.

Young Jung MD, PhD has completed his degree at the age of 26 years from Chonnam National University, Korea and postdoctoral studies from MD Anderson Cancer Center, TX. He is a Vice Dean of from Chonnam National University Medical School. He has published more than 60 papers in reputed journals and has been serving as an editorial board member of repute.

Cadmium, a widespread cumulative pollutant,is a known human carcinogen, associated withinflammation and tumor.Matrix metalloproteinase-9(MMP-9) plays a pivotal role in inflammatory reaction and tumor metastasis, however, the mechanisms underlying MMP-9 expression induced by cadmium remains obscure in human endothelial cells. Here, cadmium elevated MMP-9 expression and enzyme activity, as well as MMP-9 promoter-driven luciferase activity, in a dose and time dependent manner in ECV304 human endothelial cells. Moreover, cadmium activated phosphorylation of EGFR, Akt, Erk1/2, JNK1/2, P38MAPK and promoted NF-κB and AP-1 binding. Specific inhibition and mutagenesis study shows that EGFR, Akt, Erk1/2, JNK1/2 and transcription factor NF-κB and AP-1 were related to cadmium-induced MMP-9 expression in ECV304 cells. Furthermore, Cadmium increased ROS production and the ROS-producing NADPH oxidase. Cadmium translocates p47phox, a key subunit of NADPH oxidase, to the cell membrane. The exogenous H2O2 increased MMP-9 mRNA expression. And that, inhibition of ROS by ROS scavenger (NAC) or NADPH oxidase inhibitor (DPI) attenuated EGFR, Akt, MAPKs(Erk1/2, JNK1/2, p38 MAPK) activation, and MMP-9 expression. Likewise,inhibition of EGFR phosphorylation prevented the activation of AKT, MAPKs (Erk1/2, P38 MAPK). Finally, ECV304 cells treated with cadmium displayed markedly invasiveness, which was partially abrogated by MMP-9 neutralizing antibodies. These results demonstrated that cadmium induces MMP-9 expression via NADPH oxidase/ROS-dependent EGFR/Akt NF-кB and EGFR/MAPKs (Erk1/2, JNK1/2)/AP-1 signaling pathways and, in turn, stimulates invasiveness in human endothelial ECV304 cells. These findings provide further insight into the molecular mechanisms in the carcinogenesis effect of cadmium.

Yuh-Lin Wu has completed his PhD training in the University of Wisconsin-Madison and the postdoctoral studies in the University of North Carolina at Chapel Hill in USA. He is currently an associate professor at School of Medicine, National Yang-Ming University in Taipei, Taiwan. Dr. Wu’s lab has the major research interests in G protein signal transduction in ovary, inflammation in reproductive system and cancer progression, and anti-inflammatory molecules in treating inflammatory or cancer diseases.

Sex steroid hormones regulate multiplefemale reproductive functions. Cyclooxygenase-2 (COX-2) is an inflammation-associated enzyme to regulate prostaglandin production. Previous studies demonstrated that COX-2-deficient mice failed to ovulate, suggesting a vital role of COX-2 in ovulation. Sex steroid hormones were reported to modulate COX-2 expression: dihydrotestosterone (DHT) was able to inhibit interlukin-1 beta-induced COX-2 expression in vascular smooth muscle cells, while estradiol (E2) was able to promote COX-2 expression in the rat oviduct. In the ovary, the significance and the involving mechanisms of androgens and estrogens in COX-2 regulation remain mostly unclear. The aim of this study was to clarify whether and how sexsteroidhormones affect COX-2 expression in rat ovarian granulosa cells. Previous studies suggested that PKC could be activated by FSH or LH in follicular granulosa cells, leading to inflammatory-like consequences. Thus, a PKC activator PDD (phorbol-12, 13-didecanoate) was used in this study.It was noted that DHT appeared to attenuate PDD-induced COX-2 protein, mRNA expression and promoter activity; however, E2 was able to enhance PDD-induced COX-2 protein, mRNA expression and promoter activity. In addition, the PDD-mediated PGE2production was also impacted by DHT and E2. The PDD-mediated COX-2 expression was inhibited by parthenolide (NF-kB inhibitor), butwas enhanced by SP600125 (JNK inhibitor) or wortmannin (PI3K inhibitor). Thus, DHT and E2 may affect PKC-mediatedinflammation in ovarian granulosa cells by acting through these signaling players.

Marc Mathews completed his bachelors degree in mechanical engineering at the University of Pretoria in 2013. He is currently enrolled in his masters degree studies at the University of the North-West and is a consultant to Human-Sim (Pty) Ltd. He has published two papers on his studies in international peer reviewed journals.

Coronary heart disease (CHD) is known to be the largest cause of death globally. This is worrying when considering the substantial investments employed in the research and prevention of CHD. It may be possible that current reductionistic research techniques are not suitable in the study of CHD due to the highly interconnected nature of human biology. It may thus be possible to gain a better understanding of CHD by using a systems engineering approach to develop an integrated model of CHD. An extensive literature review was conducted to develop the integrated model. The model contains information on the pathogenesis, biomarkers, pharmaceuticals and health factors of CHD. Using the integrated model it is possible to analyse typical health factors implicated in CHD progression or mediation. Furthermore, it is possible to analyse pharmaceuticals used in CHD treatment and prevention. Analysis of the integrated model is achieved by using “connection graphs” which elucidate the interactions between health factors or pharmaceuticals and the pathogenesis of CHD through the effect on biomarkers. In this study moderate alcohol consumption and statin therapy were analysed in greater detail by quantifying the biomarker effects. The results indicate that moderate alcohol consumption could decrease CHD risk through actions on coagulation, lipid, metabolic and inflammation as indicated by biomarker quantification. Statin therapy would appear to present increases in CHD risk on coagulation, vascular function and metabolic biomarkers, while decreasing CHD risk through effects on lipid and inflammatory biomarkers.

YoungShin Song completed her Bachelor's degree at the age of 24 years from Chungnam National University and studying Master’s degree from Chungnam National University. Now, she is studying self-folding using stimuli-responsive materials

Materials that spontaneously transform into folded structures from two dimensional (2D) to three dimensional (3D) structures, in response to external stimuli, have been recently interested. Especially, stimuli-responsive materials are important as self-folding materials because these have high flexibility and responsive character to external stimuli, such as temperature, solvent, and pH. In this study, we investigate major factor of self-folding of hydrogel bilayers fabricated from simple micromolding technique with geometrical change of structures. Basically, the bilayered hydrogel microstructures are composed of responsive layer, which responses to external stimuli, and irresponsive layer. As expected, self-folding of hydrogel bilayers is driven by differential swelling property of each layer in environmental solutions. After these bilayers are exposed to specific environment, radius of curvature of self-bending curved structures shows a narrow size distribution. We characterize various parameters with respect to geometrical change of the soft-hydrogel microparticles. In conclusion, we envision that the self-actuating hydrogel materials have great potential in variety of application including actuators, drug delivery systems, tissue engineering scaffolds, valve and soft-robotic systems.

Fatma Kazdal is Masters Student in Biotechnology Program, Institute of Health Sciences, Bezmialem Vakif University.

Lots of pathological factors including Amyloid-beta (A-beta) aggregation contribute to the progression of Alzheimer’s Disease (AD). Thereby, multi-functional agents are being favored in treatment of AD in recent years. Formation of A-beta plaques are triggered mainly by divalent metals found in brain via two mechanisms. First mechanism results from lipid permeability of the metal ligand which lead to increased intracellular Cu+2 levels. The Cu+2 induces activation of Src kinase (p-src) and inhibition of protein tyrosine phosphatases (PTP) leading to phosphorylation of EGFR.Cu may also induce release of cognate EGFR ligands such as EGF or HB-EGF. Activation of EGFR induces up-regulation of ERK activity (p-ERK) and through a synergistic effect with PI3K-JNK pathway, increases metalloprotease expression. This results in increased cleavage of the A-beta peptid. Second mechanism is the interaction between two charged metal ions and A-beta, which consists of 42 amino acids, wrapped around them leading to aggregation. The use of metal chelators are required for both mechanisms. All metal chelators that are currently used has neurotoxic effects. Therefore, 25 different plant extracts which has lower toxicity possibility were investigated for Fe+2, Cu+2 and Zn+2 chelating capacity. During this process, incorrect results were obtained due to the green color of the extract. To overcome this, new methods for Zn+2 and Cu+2 binding capacity is proposed based on the shift in the UV spectrum of murexide. Results of our studies suggested that Hypericumcapitatum, Melissa officinalis, Pulicariadysenterica, Rosmarinusofficinalishave the highest metal binding activities.

Cortes Lopez obtained his degree from the City College of the City University of New York in February 2011. Since then, he has focused his professional interest on the study of the bi-directional communication of the tumor with the microenvironment. He uses biomechanical tools to explore how cells from the stromal cavity interact with the cancer cells to promote or trigger cancer development. He is a research assistant in the Cellular and Molecular Biomechanics group in the department of bioengineering at Imperial College London.

For decades, breast cancer research has focused mainly on the epithelial cells, and their transformation into malignant tumours. However, increasing evidences highlight the role of the stroma in the development of cancer. Fibroblasts, which are the major cellular component in the stroma have been found to have a paramount influence on cancer progression, and there is a growing body of evidence pointing to their role in tumour progression. Tamoxifen is an anti-estrogen drug that has been used for many years to stop epithelial cancer cell proliferation in estrogen positive breast cancer women. Intriguingly, a recent clinical trial has shown that healthy women at risk of developing breast cancer treated with tamoxifen experienced a significant reduction in their mammography density and the risk of developing breast cancer. A reduction of the mammography density correlates with changes in the rigidity of the stroma. This work unravels the biomechanical effect of Tamoxifen treatment on the behavior of the main stromal cellular components: The fibroblasts.