Sharif Digital Repository

Breast cancer is the most common malignancy in women worldwide, and is responsible for more than half a million deaths each year. The appropriate therapy depends on the evaluation of the expression of various biomarkers, such as the human epidermal growth factor receptor 2 (HER2) transmembrane protein, through specialized techniques, such as immunohistochemistry or in situ hybridization. In this work, we present the HER2 on hematoxylin and eosin (HEROHE) challenge, a parallel event of the 16th European Congress on Digital Pathology, which aimed to predict the HER2 status in breast cancer based only on hematoxylin–eosin-stained tissue samples, thus avoiding specialized techniques. The... 

It is now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and... 

Background: Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods: In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for... 

Purpose: Treatment of metastatic breast cancer patients is challenging and remains a major underlying cause of female mortality. Understanding molecular alterations in tumor development is critical to identify novel biomarkers and targets for cancer diagnosis and therapy. One of the aberrant cancer expressions gaining recent research interest is glypican-1. Several studies reported strong glypican-1 expression in various types of human cancers. However, none of these investigated glypican-1 expression in a large cohort of breast cancer histopathological subtypes. Patients and Methods: Immunohistochemistry was used to assess glypican-1 expression in 220 breast cancer patients and its relation... 

Breast and prostate cancers are common types of cancers with various strategies, such as chemotherapy and radiotherapy, for their therapy. Since these methods have undesired side effects and poor target affinity, neoteric strategies—known as aptamer-based smart drug delivery systems (SDDSs)—have been developed in recent years to overcome the obstacles of current treatment, and investigated for a clinical trial. The high affinity and versatility of aptamers for binding to the corresponding targets make them highly noticeable agents in the drug delivery domains. In addition to their exceptional benefits, aptamers are able to overcome tumor resistance because of their high selectivity and low... 

Purpose: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. Materials and Methods: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of... 

Simulating signal transduction in cellular signaling networks provides predictions of network dynamics by quantifying the changes in concentration and activity-level of the individual proteins. Since numerical values of kinetic parameters might be difficult to obtain, it is imperative to develop non-parametric approaches that combine the connectivity of a network with the response of individual proteins to signals which travel through the network. The activity levels of signaling proteins computed through existing non-parametric modeling tools do not show significant correlations with the observed values in experimental results. In this work we developed a non-parametric computational... 

Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called "adoptive cell transfer", or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least side-effects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell... 

Growth arrest-specific gene 6 (GAS6) is a growth factor-like cytokine whose function is related with vitamin K. This protein interacts with receptor tyrosine kinase proteins such as Tyro3, Axl, and TAM Receptor family, therefore affecting the tumorigenic processes via different mechanisms. GAS6-antisense 1 (GAS6-AS1) is a long non-coding RNAs (lncRNAs) that is transcribed from a genomic regions nearby GAS6. This lncRNA is also implicated in the pathobiology of cancer. We intended to judge the role of GAS6 and GAS6-AS1 in the pathogenesis of breast cancer through appraisal of their expression levels in breast cancer tissues and their paired neighboring non-cancerous samples. Expression of... 

With the passage of time and more advanced societies, there is a greater emergence and incidence of disease and necessity for improved treatments. In this respect, nowadays, aptamers, with their better efficiency at diagnosing and treating diseases than antibodies, are at the center of attention. Here, in this review, we first investigate aptamer function in various fields (such as the detection and remedy of pathogens, modification of nanoparticles, antibiotic delivery and gene delivery). Then, we present aptamer-conjugated nanocomplexes as the main and efficient factor in gene delivery. Finally, we focus on the targeted co-delivery of genes and drugs by nanocomplexes, as a new exciting...