The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual's high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients

Structure response for cellulose-based hydrogels via characterization techniques.

Hydrogels are three-dimensional crosslinked polymeric networks capable of imbibing substantial amounts of water or biological fluids and are widely used in biomedical applications, especially in pharmaceutical industry as drug delivery systems. Although their solvent content can be over 99%, hydrogels still retain the appearance and properties of solid materials and the structural response can include a smart response to environmental stimuli (pH, temp, ionic strength, electric field, presence of enzyme etc.) These responses can include shrinkage or swelling. Cellulose-based hydrogels are one of the most commonly used material and extensively investigated due to the widespread availability of cellulose in nature. Cellulose is the most abundant renewable resource on earth is intrinsically degradable. Additionally, the presence of hydroxyl groups results in fascinating structures and properties. Also, cellulose-based hydrogels with specific properties can be obtained by combining it with synthetic or natural polymers. This chapter surveys different characterization for cellulose-hydrogels and the structure response relationship. As such we would describe the techniques involved for characterizing cellulose-based hydrogels and their response in terms of their morphology such as polarized optical microscopy (POM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM); their stability by thermal properties (often with differential scanning calorimetry, DSC), structure response such as Fourier Transform Infrared Spectroscopy (FTIR), Nuclear magnetic resonance (NMR). In addition, we give a focus on measuring the mechanical properties of superabsorbent hydrogels giving examples with cellulose where applicable. Finally, we describe the techniques for analyzing biological techniques and the applications with cellulose.ye

Exclusion of chromosomal abnormalities and microdeletions 22q11 and 10p13 in algerian patients with isolated conotruncal malformation

The chromosomal abnormalities of number and structure or the 22q11.2 and 10p13-14 microdeletions are considered the main causes of congenital heart disease. In our best knowledge, cytogenetics studies on congenital heart diseases (CHD) have not been performed in Algeria. In this study, we will screen for chromosomal abnormalities and microdeletions of 22q11.2 and 10p13 in a cohort of Algerian patients. G-banded by trypsin Giemsa (GTG) and Fluorescent In Situ Hybridization (FISH) techniques have been performed to screen for chromosomal abnormalities and a critical regions 22q11.2 and 10p13-14 respectively in seventy patients with non syndromic congenital heart. GTG technique visualized no chromosomal abnormalities of number and structure in our patients. Moreover, FISH visualizing critical regions 22q11.2 and 10p13-14 respectively did not detect any microdeletion in the chromosomes 10 and 22 respectively of our patients. Our study could suggest that congenital heart defects observed in Algerian patients are not due to chromosomal abnormalities of number and structure nor the 22q11.2 and 10p13-14 microdeletions. For the fist time, we report here cytogenetics analysis of chromosomal abnormalities and the 22q11.2 and 10p13-14 microdeletions in Algerian patients with congenital heart disease. Genetic testing for screening for deletion 22q11.2 and 10p13-14 is not indicated in all patients with isolated conotruncal defects. In addition, conotruncal heart diseases have a multifactorial background like consanguinity and recessive mutations in some genes involved in cardiac morphogenesis. A genetic study to screen for the role of consanguineous marriages and some genes linked to CHD in Algerian population is on going. This study will focus also on health education for the families at risk about the importance of pre-marital genetic counseling.Хромосомные аномалии числа и структуры или микроделеции 22q11.2 и 10p13-14 считаются главными причинами врожденного порока сердца. Насколько нам известно, цитогенетические исследования врожденного порока сердца (CHD) в Алжире не проводились. В настоящей работе проведен скрининг хромосомных аномалий и микроделеций 22q11.2 и 10p13-14 в группе алжирских пациентов. Методы окраски по Гимза (GTG) и FISH были использованы для скрининга хромосомных аномалий и критичных участков 22q11.2 и 10p13-14 соответственно у 70 пациентов с несиндромным врожденным пороком сердца. GTG не выявило хромосомных аномалий по числу и структуре. Более того, изучение участков 22q11.2 и 10p13-14 не показало никаких микроделеций в хромосомах 10 и 22. Наши исследования позволяют сделать вывод, что дефекты, вызванные врожденным пороком сердца у алжирских пациентов, не связаны ни с хромосомными аномалиями числа и структуры, ни с микроделециями 22q11.2 и 10p13-14. Впервые проведен цитогенетический анализ хромосомных аномалий и микроделеций 22q11.2 и 10p13-14 у алжирских пациентов с врожденным пороком сердца. Генетическое тестирование скрининга на наличие делеций 22q11.2 и 10p13-14 не показано у всех пациентов с врожденным пороком сердца. Кроме того, конотрункальные болезни сердца имеют многофакторную основу, такую как генетическое родство и рецессивные мутации некоторых генов, вовлеченных в кардиальный морфогенез. Проводится генетическое исследование роли близкородственных браков и некоторых генов, связанных с врожденным пороком сердца, в алжирской популяции. Это исследование будет также сфокусировано на профилактической работе в семьях с факторами риска и на важности генетического консультирования перед вступлением в брак