Biorecognizable Nanoparticles Based On Hyaluronic Acid/Poly(ε-Caprolactone) Block Copolymer

Since hyaluronic acid (HA) receptor such as CD44 is over-expressed at sites of cancer cells, HA can be used as a targeting vehicles for anti-cancer drugs. The aim of this study is to synthesize block copolymer composed of hyaluronic acid and poly(ε-caprolactone) (HAPCL) and to fabricate polymeric micelles for anticancer drug targeting against CD44 receptor of tumor cells. Chemical composition of HAPCL was confirmed using 1H NMR spectroscopy. Doxorubicin (DOX) was incorporated into polymeric micelles of HAPCL. The diameters of HAPHS polymeric micelles were changed around 80nm and have spherical shapes. Targeting potential was investigated using CD44-overexpressing. When DOX-incorporated polymeric micelles was added to KB cells, they revealed strong red fluorescence color while blocking of CD44 receptor by pretreatment of free HA resulted in reduced intensity, indicating that HAPCL polymeric micelles have targetability against CD44 receptor.

Breast Cancer Treatment Evaluation based on Mammographic and Echographic Distance Computing

Accurate assessment of the primary tumor response to treatment is important in the management of breast cancer. This paper introduces a new set of treatment evaluation indicators for breast cancer cases based on the computational process of three known metrics, the Euclidian, Hamming and Levenshtein distances. The distance principals are applied to pairs of mammograms and/or echograms, recorded before and after treatment, determining a reference point in judging the evolution amount of the studied carcinoma. The obtained numerical results are indeed very transparent and indicate not only the evolution or the involution of the tumor under treatment, but also a quantitative measurement of the benefit in using the selected method of treatment.

Segmentation of Lungs from CT Scan Images for Early Diagnosis of Lung Cancer

Segmentation is an important step in medical image analysis and classification for radiological evaluation or computer aided diagnosis. The CAD (Computer Aided Diagnosis ) of lung CT generally first segment the area of interest (lung) and then analyze the separately obtained area for nodule detection in order to diagnosis the disease. For normal lung, segmentation can be performed by making use of excellent contrast between air and surrounding tissues. However this approach fails when lung is affected by high density pathology. Dense pathologies are present in approximately a fifth of clinical scans, and for computer analysis such as detection and quantification of abnormal areas it is vital that the entire and perfectly lung part of the image is provided and no part, as present in the original image be eradicated. In this paper we have proposed a lung segmentation technique which accurately segment the lung parenchyma from lung CT Scan images. The algorithm was tested against the 25 datasets of different patients received from Ackron Univeristy, USA and AGA Khan Medical University, Karachi, Pakistan.

Superior Performances of the Neural Network on the Masses Lesions Classification through Morphological Lesion Differences

Purpose of this work is to develop an automatic classification system that could be useful for radiologists in the breast cancer investigation. The software has been designed in the framework of the MAGIC-5 collaboration. In an automatic classification system the suspicious regions with high probability to include a lesion are extracted from the image as regions of interest (ROIs). Each ROI is characterized by some features based generally on morphological lesion differences. A study in the space features representation is made and some classifiers are tested to distinguish the pathological regions from the healthy ones. The results provided in terms of sensitivity and specificity will be presented through the ROC (Receiver Operating Characteristic) curves. In particular the best performances are obtained with the Neural Networks in comparison with the K-Nearest Neighbours and the Support Vector Machine: The Radial Basis Function supply the best results with 0.89 ± 0.01 of area under ROC curve but similar results are obtained with the Probabilistic Neural Network and a Multi Layer Perceptron.

Oncogene Identification using Filter based Approaches between Various Cancer Types in Lung

Lung cancer accounts for the most cancer related deaths for men as well as for women. The identification of cancer associated genes and the related pathways are essential to provide an important possibility in the prevention of many types of cancer. In this work two filter approaches, namely the information gain and the biomarker identifier (BMI) are used for the identification of different types of small-cell and non-small-cell lung cancer. A new method to determine the BMI thresholds is proposed to prioritize genes (i.e., primary, secondary and tertiary) using a k-means clustering approach. Sets of key genes were identified that can be found in several pathways. It turned out that the modified BMI is well suited for microarray data and therefore BMI is proposed as a powerful tool for the search for new and so far undiscovered genes related to cancer.

Genetic Polymorphism of the Acute Lymphoblastic Leukaemia and Hyperhomocysteinemia its Relation with the for a Group of Children in the East of Algeria

A lot of recent research have spoken on the relation between the increase of the homocysteinemia and some kinds of cancer . For that, our study was based on the research of a possible relation between the increase of the concentration of this amino-acid in the plasma and the appearance of the disease of the Acute Lymphoblastic Leukaemia in a part of Algerian children with Berber origin in the East of Algeria . The study has done on 47 ill persons with an average age of (09±06 ) years , with whom the disease has diagnosed by blood and marrow examination in the hospital of blood diseases in the CHU of Batna, and on 194 healthy witnesses of the same age. The two groups were benefited by a dosage of the concentration of the homocysteine vitamin B9 ,vitamin B12 , and also of the study of special polymorphisms of indispensable enzymes in the metabolism of this acid , and that by the use of the method ( Light cycler ) Real time PCR , on the following enzymes : MS ( C2756G ), MSR ( A66G ) ,MTHFR1 ( C677T ) and MTHFR2 (A1298C). The obtained results have revealed that the rate of the homozygote muted genotype is the less frequent in the two groups , and that exist at list one genotype of each enzyme in the ill group and in which the percentage exceed with remarkable way the same genotype in the healthy group and we notice specially the muted genotype GG of -the methionine synthetase-and the form TT of the enzyme – methyline tetra hydrofolate reductase – We notice the existence of considerable number of genotypes in the ill group lied with characteristic increase of this Amino-acid ,and that for the reduction of the biologic activity of these enzymes which become inefficient in the transfer of the homocysteine into the methionine and cause the diminution of the biologic activity of these enzymes and with consequence the reduction of the percentage of methylic radicals in the DNA of studied genes and that lead to the increase of the activity and the capacity of transcription , and it-s so probably that this last one is one of the factors of this disease especially if we know that the specific check-up of vitamins is normal and similar in the two groups , which ovoid the hypothesis of the reduction of vitamins . We notice also that the heterozygote genotype is the less in the sick category except the MTHFR2. Wild genotype is more frequent in the witness group except MSR. Even these results are partials; they open a new way in the genetic diagnosis of this malicious disease which allow a precocious diagnosis and the use of an effective and appropriated treatment in the same time.

Study of Encapsulation of Quantum Dots in Polystyrene and Poly (E-Caprolactone)Microreactors Prepared by Microvolcanic Eruption of Freeze Dried Microspheres

Polymeric microreactors have emerged as a new generation of carriers that hold tremendous promise in the areas of cancer therapy, controlled delivery of drugs, for removal of pollutants etc. Present work reports a simple and convenient methodology for synthesis of polystyrene and poly caprolactone microreactors. An aqueous suspension of carboxylated (1μm) polystyrene latex particles was mixed with toluene solution followed by freezing with liquid nitrogen. Freezed particles were incubated at -20°C and characterized for formation of voids on the surface of polymer microspheres by Field Emission Scanning Electron Microscope. The hollow particles were then overnight incubated at 40ºC with unfunctionalized quantum dots (QDs) in 5:1 ratio. QDs Encapsulated polystyrene microcapsules were characterized by fluorescence microscopy. Likewise Poly ε-caprolactone microreactors were prepared by micro-volcanic rupture of freeze dried microspheres synthesized using emulsification of polymer with aqueous Poly vinyl alcohol and freezed with liquid nitrogen. Microreactors were examined with Field Emission Scanning Electron Microscope for size and morphology. Current study is an attempt to create hollow polymer particles which can be employed for microencapsulation of nanoparticles and drug molecules.

Parametric and Nonparametric Analysis of Breast Cancer Treatments

The objective of the present research manuscript is to perform parametric, nonparametric, and decision tree analysis to evaluate two treatments that are being used for breast cancer patients. Our study is based on utilizing real data which was initially used in “Tamoxifen with or without breast irradiation in women of 50 years of age or older with early breast cancer" [1], and the data is supplied to us by N.A. Ibrahim “Decision tree for competing risks survival probability in breast cancer study" [2]. We agree upon certain aspects of our findings with the published results. However, in this manuscript, we focus on relapse time of breast cancer patients instead of survival time and parametric analysis instead of semi-parametric decision tree analysis is applied to provide more precise recommendations of effectiveness of the two treatments with respect to reoccurrence of breast cancer.

Automatic Detection of Mass Type Breast Cancer using Texture Analysis in Korean Digital Mammography

In this study, we present an advanced detection technique for mass type breast cancer based on texture information of organs. The proposed method detects the cancer areas in three stages. In the first stage, the midpoints of mass area are determined based on AHE (Adaptive Histogram Equalization). In the second stage, we set the threshold coefficient of homogeneity by using MLE (Maximum Likelihood Estimation) to compute the uniformity of texture. Finally, mass type cancer tissues are extracted from the original image. As a result, it was observed that the proposed method shows an improved detection performance on dense breast tissues of Korean women compared with the existing methods. It is expected that the proposed method may provide additional diagnostic information for detection of mass-type breast cancer.

Oral Cancer Screening Intentions of Residents in Eastern Taiwan

The incidence of oral cancer in Taiwan increased year by year. It replaced the nasopharyngeal as the top incurrence among head and neck cancers since 1994. Early examination and earlier identification for earlier treatment is the most effective medical treatment for these cancers. Although the government fully subsidized the expenses with tremendous promotion program for oral cancer screening, the citizen-s participation remained low. Purpose of this study is to understand the factors affecting the citizens- behavior intensions of taking an oral cancer screening. Based on the Theory of Planned Behavior, this study adopted four distinctive variables in explaining the captioned behavior intentions.700 questionnaires were dispatched with 500 valid responses or 71.4% returned by the citizens with an age 30 or above from the eastern counties of Taiwan. Test results has shown that attitude toward, subjective norms of, and perceived behavioral control over the oral cancer screening varied from some demographic factors to another. The study proofed that attitude toward, subjective norms of, and perceived behavioral control over the oral cancer screening had positive impacts on the corresponding behavior intention. The test concluded that the theory of planned behavior was appropriate as a theoretical framework in explaining the influencing factors of intentions of taking oral cancer screening. This study suggested the healthcare professional should provide high accessibility of screening services other than just delivering knowledge on oral cancer to promote the citizens- intentions of taking the captioned screening. This research also provided a practical implication to the healthcare professionals when formulating and implementing promotion instruments for lifting the screening rate of oral cancer.

Bioinformatics Profiling of Missense Mutations

The ability to distinguish missense nucleotide substitutions that contribute to harmful effect from those that do not is a difficult problem usually accomplished through functional in vivo analyses. In this study, instead current biochemical methods, the effects of missense mutations upon protein structure and function were assayed by means of computational methods and information from the databases. For this order, the effects of new missense mutations in exon 5 of PTEN gene upon protein structure and function were examined. The gene coding for PTEN was identified and localized on chromosome region 10q23.3 as the tumor suppressor gene. The utilization of these methods were shown that c.319G>A and c.341T>G missense mutations that were recognized in patients with breast cancer and Cowden disease, could be pathogenic. This method could be use for analysis of missense mutation in others genes.

PMF, Cesium and Rubidium Nanoparticles Induce Apoptosis in A549 Cells

Cancer becomes one of the leading cause of death in many countries over the world. Fourier-transform infrared (FTIR) spectra of human lung cancer cells (A549) treated with PMF (natural product extracted from PM 701) for different time intervals were examined. Second derivative and difference method were taken in comparison studies. Cesium (Cs) and Rubidium (Rb) nanoparticles in PMF were detected by Energy Dispersive X-ray attached to Scanning Electron Microscope SEM-EDX. Characteristic changes in protein secondary structure, lipid profile and changes in the intensities of DNA bands were identified in treated A549 cells spectra. A characteristic internucleosomal ladder of DNA fragmentation was also observed after 30 min of treatment. Moreover, the pH values were significantly increases upon treatment due to the presence of Cs and Rb nanoparticles in the PMF fraction. These results support the previous findings that PMF is selective anticancer agent and can produce apoptosis to A549 cells.

Rigorous Electromagnetic Model of Fourier Transform Infrared (FT-IR) Spectroscopic Imaging Applied to Automated Histology of Prostate Tissue Specimens

Fourier transform infrared (FT-IR) spectroscopic imaging is an emerging technique that provides both chemically and spatially resolved information. The rich chemical content of data may be utilized for computer-aided determinations of structure and pathologic state (cancer diagnosis) in histological tissue sections for prostate cancer. FT-IR spectroscopic imaging of prostate tissue has shown that tissue type (histological) classification can be performed to a high degree of accuracy [1] and cancer diagnosis can be performed with an accuracy of about 80% [2] on a microscopic (≈ 6μm) length scale. In performing these analyses, it has been observed that there is large variability (more than 60%) between spectra from different points on tissue that is expected to consist of the same essential chemical constituents. Spectra at the edges of tissues are characteristically and consistently different from chemically similar tissue in the middle of the same sample. Here, we explain these differences using a rigorous electromagnetic model for light-sample interaction. Spectra from FT-IR spectroscopic imaging of chemically heterogeneous samples are different from bulk spectra of individual chemical constituents of the sample. This is because spectra not only depend on chemistry, but also on the shape of the sample. Using coupled wave analysis, we characterize and quantify the nature of spectral distortions at the edges of tissues. Furthermore, we present a method of performing histological classification of tissue samples. Since the mid-infrared spectrum is typically assumed to be a quantitative measure of chemical composition, classification results can vary widely due to spectral distortions. However, we demonstrate that the selection of localized metrics based on chemical information can make our data robust to the spectral distortions caused by scattering at the tissue boundary.

Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells

This study determines the effect of naked and heparinbased super-paramagnetic iron oxide nanoparticles on the human cancer cell lines of A2780. Doxorubicin was used as the anticancer drug, entrapped in the SPIO-NPs. This study aimed to decorate nanoparticles with heparin, a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. The nanoparticles containing the anticancer drug DOX were prepared by a solvent evaporation and emulsification cross-linking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of DOX from the SPIO-NPs was successful. Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell toxicity than the individual HP and confocal microscopy analysis confirmed excellent cellular uptake efficiency. These results indicate that HP based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Evolutionary of Prostate Cancer Stem Cells in Prostate Duct

A systems approach model for prostate cancer in prostate duct, as a sub-system of the organism is developed. It is accomplished in two steps. First this research work starts with a nonlinear system of coupled Fokker-Plank equations which models continuous process of the system like motion of cells. Then extended to PDEs that include discontinuous processes like cell mutations, proliferation and deaths. The discontinuous processes is modeled by using intensity poisson processes. The model incorporates the features of the prostate duct. The system of PDEs spatial coordinate is along the proximal distal axis. Its parameters depend on features of the prostate duct. The movement of cells is biased towards distal region and mutations of prostate cancer cells is localized in the proximal region. Numerical solutions of the full system of equations are provided, and are exhibit traveling wave fronts phenomena. This motivates the use of the standard transformation to derive a canonically related system of ODEs for traveling wave solutions. The results obtained show persistence of prostate cancer by showing that the non-negative cone for the traveling wave system is time invariant. The traveling waves have a unique global attractor is proved also. Biologically, the global attractor verifies that evolution of prostate cancer stem cells exhibit the avascular tumor growth. These numerical solutions show that altering prostate stem cell movement or mutation of prostate cancer cells lead to avascular tumor. Conclusion with comments on clinical implications of the model is discussed.

Gene Selection Guided by Feature Interdependence

Cancers could normally be marked by a number of differentially expressed genes which show enormous potential as biomarkers for a certain disease. Recent years, cancer classification based on the investigation of gene expression profiles derived by high-throughput microarrays has widely been used. The selection of discriminative genes is, therefore, an essential preprocess step in carcinogenesis studies. In this paper, we have proposed a novel gene selector using information-theoretic measures for biological discovery. This multivariate filter is a four-stage framework through the analyses of feature relevance, feature interdependence, feature redundancy-dependence and subset rankings, and having been examined on the colon cancer data set. Our experimental result show that the proposed method outperformed other information theorem based filters in all aspect of classification errors and classification performance.

Automated Knowledge Engineering

This article outlines conceptualization and implementation of an intelligent system capable of extracting knowledge from databases. Use of hybridized features of both the Rough and Fuzzy Set theory render the developed system flexibility in dealing with discreet as well as continuous datasets. A raw data set provided to the system, is initially transformed in a computer legible format followed by pruning of the data set. The refined data set is then processed through various Rough Set operators which enable discovery of parameter relationships and interdependencies. The discovered knowledge is automatically transformed into a rule base expressed in Fuzzy terms. Two exemplary cancer repository datasets (for Breast and Lung Cancer) have been used to test and implement the proposed framework.

A Systems Approach to Gene Ranking from DNA Microarray Data of Cervical Cancer

In this paper we present a method for gene ranking from DNA microarray data. More precisely, we calculate the correlation networks, which are unweighted and undirected graphs, from microarray data of cervical cancer whereas each network represents a tissue of a certain tumor stage and each node in the network represents a gene. From these networks we extract one tree for each gene by a local decomposition of the correlation network. The interpretation of a tree is that it represents the n-nearest neighbor genes on the n-th level of a tree, measured by the Dijkstra distance, and, hence, gives the local embedding of a gene within the correlation network. For the obtained trees we measure the pairwise similarity between trees rooted by the same gene from normal to cancerous tissues. This evaluates the modification of the tree topology due to progression of the tumor. Finally, we rank the obtained similarity values from all tissue comparisons and select the top ranked genes. For these genes the local neighborhood in the correlation networks changes most between normal and cancerous tissues. As a result we find that the top ranked genes are candidates suspected to be involved in tumor growth and, hence, indicates that our method captures essential information from the underlying DNA microarray data of cervical cancer.

Gene Expression Signature for Classification of Metastasis Positive and Negative Oral Cancer in Homosapiens

Cancer classification to their corresponding cohorts has been key area of research in bioinformatics aiming better prognosis of the disease. High dimensionality of gene data has been makes it a complex task and requires significance data identification technique in order to reducing the dimensionality and identification of significant information. In this paper, we have proposed a novel approach for classification of oral cancer into metastasis positive and negative patients. We have used significance analysis of microarrays (SAM) for identifying significant genes which constitutes gene signature. 3 different gene signatures were identified using SAM from 3 different combination of training datasets and their classification accuracy was calculated on corresponding testing datasets using k-Nearest Neighbour (kNN), Fuzzy C-Means Clustering (FCM), Support Vector Machine (SVM) and Backpropagation Neural Network (BPNN). A final gene signature of only 9 genes was obtained from above 3 individual gene signatures. 9 gene signature-s classification capability was compared using same classifiers on same testing datasets. Results obtained from experimentation shows that 9 gene signature classified all samples in testing dataset accurately while individual genes could not classify all accurately.

New Device for Enhancement of Liposomal Magnetofection Efficiency of Cancer Cells

Liposomal magnetofection is the most powerful nonviral method for the nucleic acid delivery into the cultured cancer cells and widely used for in vitro applications. Use of the static magnetic field condition may result in non-uniform distribution of aggregate complexes on the surface of cultured cells. To prevent this, we developed the new device which allows to concentrate aggregate complexes under dynamic magnetic field, assisting more contact of these complexes with cellular membrane and, possibly, stimulating endocytosis. Newly developed device for magnetofection under dynamic gradient magnetic field, “DynaFECTOR", was used to compare transfection efficiency of human liver hepatocellular carcinoma cell line HepG2 with that obtained by lipofection and magnetofection. The effect of two parameters on transfection efficiency, incubation time under dynamic magnetic field and rotation frequency of magnet, was estimated. Liposomal magnetofection under dynamic gradient magnetic field showed the highest transfection efficiency for HepG2 cells.