TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway.

Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed.

Application of aptamers in treatment and diagnosis of leukemia.

Leukemia is a cancer of blood cells and bone marrow, leading to death in many patients mainly in children. Over the last several years, aptamers generated by SELEX (Systematic evolution of ligands by exponential enrichment) method, have quickly become a new class of targeting ligands for drug delivery applications and recently have been widely exploited in different biomedical applications, due to several potent properties such as high binding affinity and selectivity, low or no immunogenicity and toxicity, low cost and thermal stability. In this review, we presented in details about aptamers involved in targeting, and treatment of leukemia.

Efficient megalin targeted delivery to renal proximal tubular cells mediated by modified-polymyxin B-polyethylenimine based nano-gene-carriers.

Non-viral vectors have attracted great interest, as they are simple to prepare, easy to modify and relatively safe, compared to viral vectors. Kidney-targeted gene delivery systems depict a promising technology to improve drug efficacy in renal diseases treatments. In order to develop a novel kidney-targeted gene delivery system, we synthesized polyamine-PEI conjugates using polymyxin B as ligand and investigated their potential targeting efficiency.

evaluation of dihydropyridine-3-carbonitriles as potential cytotoxic agents through PIM-1 protein kinase inhibition.

PIM-1 protein kinase inhibitor belongs to a novel class of serine/threonine kinases. As PIM-1 is overexpressed in cancer cells and possesses oncogenic functions, its inhibition provides a new option in cancer therapy. In this study, inhibitory effects of seven analogues of 1, 2-dihydropyridine-3-carbonitrile derivatives , on the activity of recombinant PIM-1 were evaluated using dimethylthiazol diphenyltetrazolium bromide (MTT) assay.

Correlation of Gankyrin oncoprotein overexpression with histopathological grade in prostate cancer.

Prostate cancer is the second most commonly diagnosed cancer among men worldwide. Identifying new prognostic and predictive biomarkers will help stratification of prostate cancer patients for a better treatment. Gankyrin is a novel oncoprotein which regulates cell cycle and protein degradation.

The Cardiotoxic Mechanism of Doxorubicin (DOX) and Pegylated Liposomal DOX in Mice Bearing C-26 Colon Carcinoma: a Study Focused on microRNA Role for Toxicity Assessment of New Formulations.

Purpose: MicroRNAs (miRs) are a group of small non-coding RNAs that regulate transcriptional or post-transcriptional gene expression. The aim of the present study was to investigate the role of miR -1, -21 and -145 and their targets in cardiotoxicity-induced by DOX and pegylated liposomal DOX.

Methods: BALB/c mice subjected to subcutaneous injection of C-26 tumor cells.

Identification and imaging of leukemia cells using dual-aptamer-functionalized graphene oxide complex.

Acute lymphoblastic leukemia is the most common malignancy in children. Patient improvement completely depends on the diagnosis of acute lymphoblastic leukemia. So there is a great demand for diagnosis of acute lymphoblastic leukemia.

Synthesis of theranostic epithelial cell adhesion molecule targeted mesoporous silica nanoparticle with gold gatekeeper for hepatocellular carcinoma.

Aim: In this study, we report the fabrication of epithelial cell adhesion molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for theranostic applications.

Materials & Methods: The prepared targeted and nontargeted formulations were evaluated in vitro in terms of their cellular internalization and toxicity. The prepared theranostic hybrid system was also implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo.

High level expression of recombinant human growth hormone in : crucial role of translation initiation region.

For high-throughput production of recombinant protein in (), besides important parameters such as efficient vector with strong promoter and compatible host, other important issues including codon usage, rare codons, and GC content specially at N-terminal region should be considered. In the current study, the effect of decreasing the percentage of GC nucleotides and optimizing codon usage at N-terminal region of human growth hormone (hGH) cDNA on the level of its expression in were investigated. Mutation in cDNA of hGH was performed through site-directed mutagenesis using PCR.

A new chemotherapy agent-free theranostic system composed of graphene oxide nano-complex and aptamers for treatment of cancer cells.

The common cancer treatment strategies like chemotherapy and radiotherapy are nonspecific and can trigger severe side effects by damaging normal cells. So, targeted cancer therapies, such as apoptosis induction, have attracted great attention in recent years. In this project, two nano-complexes, MUC1 aptamer-NAS-24 aptamer-Graphene oxide (GO) and MUC1 aptamer-Cytochrome C aptamer-GO, were designed to induce cell programmed death in MDA-MB-231 and MCF-7 cells (breast cancer cell lines) and to verify the level of apoptosis in both cell lines.

A novel chemotherapy drug-free delivery system composed of three therapeutic aptamers for the treatment of prostate and breast cancers in vitro and in vivo.

In this study, a novel chemotherapy drug-free DNA nanocomplex composed of three therapeutic aptamers (IDA, AS1411 and apMNK2F) was designed for treatment of cancer cells. For MTT assay, PC-3 and 4T1 cells (target cells) and CHO cells (nontarget cells) were treated with apMNK2F-AS1411-IDA complex (DNA nanocomplex), as well as AS1411, IDA and apMNK2F alone. Internalization of apMNK2F-AS1411-IDA complex was analyzed by fluorescence imaging and flow cytometry analysis.

Chitosan-modified PLGA nanoparticles tagged with 5TR1 aptamer for in vivo tumor-targeted drug delivery.

In this study, we reported epirubicin (Epi) encapsulated nanoparticles (NPs) formulated with biocompatible and biodegradable poly (lactic-co-glycolic acid) (PLGA) modified with chitosan (CS) through a physical adsorption method. Using chitosan, the solubility and surface charge of PLGA was modified to make efficient drug carriers for cancer cells. To improve the anti-tumor efficacy, we developed targeted therapy of tumor cells using a 5TR1 DNA aptamer (Apt) against the MUC1 receptor.

Comparative proteome analysis of human esophageal cancer and adjacent normal tissues.

Objectives: Ranking as the sixth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death worldwide. One of the main reasons for the low survival of patients with esophageal cancer is its late diagnosis.

Materials And Methods: We used proteomics approach to analyze ESCC tissues with the aim of a better understanding of the malignant mechanism and searching candidate protein biomarkers for early diagnosis of esophageal cancer.

Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents.

Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors.

Megalin-targeted enhanced transfection efficiency in cultured human HK-2 renal tubular proximal cells using aminoglycoside-carboxyalkyl- polyethylenimine -containing nanoplexes.

Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI (25kDa PEI) or carboxyalkylated-PEI (10kDa PEI).

A new amplified π-shape electrochemical aptasensor for ultrasensitive detection of aflatoxin B.

There is a prompt need for determination of aflatoxin B (AFB) in food products to avoid distribution and consumption of contaminated food products. In this study, an accurate electrochemical sensing strategy was presented for detection of AFB based on aptamer (Apt)-complementary strands of aptamer (CSs) complex which forms a π-shape structure on the surface of electrode and exonuclease I (Exo I). The presence of π-shape structure as a double-layer physical barrier allowed detection of AFB with high sensitivity.

Optical and Electrochemical Aptasensors for Sensitive Detection of Streptomycin in Blood Serum and Milk.

Detection and quantitation of antibiotic residues in blood serum and foodstuffs are in great demand. We have developed aptasensors for detection of streptomycin using electrochemical and optical methods. In the first method, an electrochemical aptasensor was developed for sensitive and selective detection of streptomycin, based on combination of exonuclease I (Exo I), complementary strand of aptamer (CS), arch shaped structure of aptamer (Apt)-CS conjugate, and gold electrode.

A novel fluorescent aptasensor for ultrasensitive detection of microcystin-LR based on single-walled carbon nanotubes and dapoxyl.

To assure water safety and protect human health, precise and simple analytical approaches are highly desired to determine low concentrations of microcystin-leucine-arginine (MC-LR), a toxin, in both water and serum samples. Herein, a simple, rapid and accurate aptamer-based fluorescent sensor was used for selective recognition of MC-LR, based on single-walled carbon nanotubes (SWNTs) as immobilizers, dapoxyl as a fluorescent dye, DAP-10 as a specific aptamer for dapoxyl and unmodified MC-LR aptamer (Apt) as a sensing ligand. The sensing method was developed to produce a remarkable fluorescence intensity difference in the absence and presence of MC-LR.

Promising gene delivery system based on polyethylenimine-modified silica nanoparticles.

This article reports on the synthesis and full characterization of innovative silica-based nanoparticle composed of fumed silica as a core decorated with polyethylenimine (PEI) with different molecular weights (25, 10 and 1.8 kDa). Wide range of analytical, spectroscopic, and microscopic methods (TEM, DLS, ζ potential, elemental analysis (EA), TNBS and FTIR) were used to characterize the nanoparticles.

Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.

Biocompatible polymersomes-based cancer theranostics: Towards multifunctional nanomedicine.

Polymersomes are polymeric vesicles that have numerous advantages for theranostics, the integrated approach of therapeutics and diagnostics. Polymersomes possess core- shell structures which encapsulate hydrophilic molecules in the aqueous compartment and hydrophobic molecules in the bilayer of the vesicles. Polymersomes are made of different amphiphilic block copolymers.

The intracellular delivery of plasmid DNA using cationic reducible carbon nanotube - Disulfide conjugates of polyethylenimine.

A series of polyethylenimine conjugates of single-walled carbon nanotube (PEI-SWNT) containing bioreducible disulfide bonds was synthesized and evaluated for their transfection efficiency. Different molecular weights of polyethylenimine (PEI) were thiolated with different mole ratio of 2-iminothiolane (2-IT). Single-walled carbon nanotube (SWNT) was first carboxylated and then three different cysteine-functionalized SWNT formulations were synthesized via introduced linkers: a) carbonyl group b) spermidine c) 1,8-diamino 3,6-dioxo octane.

The effects of polyethylenimine/DNA nanoparticle on transcript levels of apoptosis-related genes.

Context: Polyethylenimine (PEI) is a cationic polymer commonly used in gene transfer. Although numerous investigations have indicated that PEI can induce apoptosis/necrosis but the mechanism of its cytotoxicity is still poorly understood.

Objective: The purpose of this study was to investigate the effects of PEI/DNA complexes on the expression of apoptotic genes in human colon adenocarcinoma cells (HT29).

Inhibition of Akt phosphorylation attenuates resistance to TNF-α cytotoxic effects in MCF-7 cells, but not in their doxorubicin resistant derivatives.

Objectives: Acquisition of TNF-α resistance plays role in the onset and growth of malignant tumors. Previous studies have demonstrated that MCF-7 cell line and its doxorubicin resistant variant MCF-7/Adr are resistant against the cytotoxic effects of TNF-α. In this study, we investigated the role of Akt activation in resistance of MCF-7 and MCF-7/Adr against TNF-α cytotoxicity.

A novel atheroprotective role of MF59-like adjuvant when co-administered with CETP vaccine in rabbit model of atherosclerosis.

Objectives: In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice.

Materials And Methods: Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis.