Publications by authors named "Behrouz Farhadihosseinabadi"

12 Publications

  • Page 1 of 1

PI3 kinase signaling pathway in hematopoietic cancers: A glance in miRNA's role.

J Clin Lab Anal 2021 Apr 5;35(4):e23725. Epub 2021 Mar 5.

Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Hematopoietic cancers are among the most common malignancies worldwide, which are divided into different types depending on the origin of tumor cells. In recent years, the pivotal role of different signaling pathways in the onset and progression of these cancer types has been well established. One of these pathways, whose role in blood malignancies has been well-defined, is PI3K/mTOR/AKT axis. The signaling pathway involves in a wide variety of important biological events in cells. It is clear that dysregulation of mediators involved in PI3 kinase signaling takes a pivotal role in cancer development. Considering the undeniable role of miRNAs, as one of the well-known families of non-coding RNAs, in gene regulation, we aimed to review the role of miRNAs in regulation of PI3 kinase signaling effectors in hematopoietic cancers.
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http://dx.doi.org/10.1002/jcla.23725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059748PMC
April 2021

Human amniotic mesenchymal stem cells to promote/suppress cancer: two sides of the same coin.

Stem Cell Res Ther 2021 Feb 12;12(1):126. Epub 2021 Feb 12.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Cancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitable reservoir. There are conflicting opinions about the role of human amniotic membrane/fluid mesenchymal stem cells (hAMSCS/hAFMSCs) in cancer, as some studies demonstrating the anticancer effects of these cells and others suggesting their progressive effects on cancer. This review focuses on recent findings about the role of hAMSCs/hAFMSCs in cancer treatment and summarizes the suppressing as well as promoting effects of these cells on cancer progression and underling mechanisms.
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http://dx.doi.org/10.1186/s13287-021-02196-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881457PMC
February 2021

Key Regulatory miRNAs and their Interplay with Mechanosensing and Mechanotransduction Signaling Pathways in Breast Cancer Progression.

Mol Cancer Res 2020 08 19;18(8):1113-1128. Epub 2020 May 19.

Genetics and Biotechnology Lab, Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

According to the WHO, breast cancer is the most common cancer in women worldwide. Identification of underlying mechanisms in breast cancer progression is the main concerns of researches. The mechanical forces within the tumor microenvironment, in addition to biochemical stimuli such as different growth factors and cytokines, activate signaling cascades, resulting in various changes in cancer cell physiology. Cancer cell proliferation, invasiveness, migration, and, even, resistance to cancer therapeutic agents are changed due to activation of mechanotransduction signaling. The mechanotransduction signaling is frequently dysregulated in breast cancer, indicating its important role in cancer cell features. So far, a variety of experimental investigations have been conducted to determine the main regulators of the mechanotransduction signaling. Currently, the role of miRNAs has been well-defined in the cancer process through advances in molecular-based approaches. miRNAs are small groups of RNAs (∼22 nucleotides) that contribute to various biological events in cells. The central role of miRNAs in the regulation of various mediators involved in the mechanotransduction signaling has been well clarified over the last decade. Unbalanced expression of miRNAs is associated with different pathologic conditions. Overexpression and downregulation of certain miRNAs were found to be along with dysregulation of mechanotransduction signaling effectors. This study aimed to critically review the role of miRNAs in the regulation of mediators involved in the mechanosensing pathways and clarify how the cross-talk between miRNAs and their targets affect the cell behavior and physiology of breast cancer cells.
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http://dx.doi.org/10.1158/1541-7786.MCR-19-1229DOI Listing
August 2020

Comparative immunomodulatory properties of mesenchymal stem cells derived from human breast tumor and normal breast adipose tissue.

Cancer Immunol Immunother 2020 Sep 30;69(9):1841-1854. Epub 2020 Apr 30.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: Mesenchymal stem cells (MSCs), one of the most important stromal cells in the tumor microenvironment, play a major role in the immunomodulation and development of tumors. In contrast to immunomodulatory effects of bone marrow-derived MSCs, resident MSCs were not well studied in tumor. The aim of this study was to compare the immunomodulatory properties and protein secretion profiles of MSCs isolated from breast tumor (T-MSC) and normal breast adipose tissue (N-MSC).

Materials And Methods: T-MSCs and N-MSCs were isolated by the explant culture method and characterized, and their immunomodulatory function was assessed on peripheral blood lymphocytes (PBLs) by evaluating the effects of MSC conditioned media on the proliferation and induction of some cytokines and regulatory T cells (Tregs) by BrdU assay, ELISA, and flow cytometry. In addition, we compared the secretion of indoleamine 2,3-dioxygenase (IDO), vascular endothelial growth factor (VEGF), matrix metallopeptidase (MMP)-2, MMP-9, and Galectin-1.

Results: T-MSCs showed a higher secretion of transforming growth factor beta (TGF-β), prostaglandin E2 (PGE2), IDO, and VEGF and lower secretion of MMP-2 and MMP-9 compared with N-MSCs. However, no significant difference was found in the secretion of interferon gamma (IFN-γ), interleukin 10 (IL10), IL4, IL17, and Galectin-1 in T-MSCs and N-MSCs. The immunomodulatory effect of soluble factors on PBLs showed that T-MSCs, in contrast to N-MSCs, stimulate PBL proliferation. Importantly, the ability of T-MSCs to induce IL10, TGF-β, IFN-γ, and PGE2 was higher than that of N-MSCs. In addition, T-MSCs and N-MSCs exhibited no significant difference in Treg induction.

Conclusion: MSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions.
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http://dx.doi.org/10.1007/s00262-020-02567-yDOI Listing
September 2020

HSP90 and Co-chaperones: Impact on Tumor Progression and Prospects for Molecular-Targeted Cancer Therapy.

Cancer Invest 2020 May 27;38(5):310-328. Epub 2020 Apr 27.

Department of Tissue engineering and applied cell, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Heat shock protein 90 (HSP90), a highly and unique chaperone, presents as a double-edged sword. It plays an essential role in many physiological and pathological processes, including tumor development. The current review highlights a recent understanding of the roles of HSP90 in molecular mechanisms underlying cancer survival and progression. HSP90 and its client proteins through the regulation of oncoproteins including signaling proteins, receptors, and transcriptional factors involved in tumorigenesis. It also has potential clinical application as diagnostic and prognostic biomarkers for assessing cancer progression. In this way, using HSP90 to develop new anticancer therapeutic agents including HSP90 inhibitors, anti-HSP90 antibody, and HSP90-based vaccines has been promising.
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http://dx.doi.org/10.1080/07357907.2020.1752227DOI Listing
May 2020

The in vivo effect of Lacto-N-neotetraose (LNnT) on the expression of type 2 immune response involved genes in the wound healing process.

Sci Rep 2020 01 22;10(1):997. Epub 2020 Jan 22.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Lacto-n-neotatraose (LNnT) oligosaccharide shows properties such as anti-inflammatory, type 2 immune response induction, induced angiogenesis, and anti-bacterial effects. Here, we hypothesized that the application of LnNT in the skin full-thickness wound can accelerate the healing process through its anti-inflammatory effect as well as induction of type 2 immune responses. In this study, we evaluated the cell viability of fibroblasts in the presence of LNnT. The full-thickness wound model was created by punch biopsy. The mice were treated intradermaly with LNnT at the concentrations of 100 and 200 µg or PBS as a control group. The wounds samples were compared based on the macroscopic and histological evaluations. The amount of collagen deposition and expression of genes involved in type 2 immunity were measured by the hydroxyproline assay and real time PCR method, respectively. Our results showed that LNnT had no negative effect on the cell viability of fibroblasts. LNnT increased the wound closure rate on day 7 post-wounding. H&E stain analysis revealed that mice treated with 200 µg LNnT exhibited better healing score, follicle formation, and lower epidermal thickness index. The mice treated with LNnT exhibited a lower collagen deposition on day 21 and higher collagen content on days 7 and 14 post-treatment. The LNnT groups also exhibited a lower number of neutrophils and a higher number of basal cells and fibroblasts. The expression rate of IL-10, IL-4, and IL-13 was higher in the LNnT groups. These results showed the high potential of LNnT for use in treatment of full-thickness wounds.
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http://dx.doi.org/10.1038/s41598-020-57860-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976585PMC
January 2020

Inducing type 2 immune response, induction of angiogenesis, and anti-bacterial and anti-inflammatory properties make Lacto-n-Neotetraose (LNnT) a therapeutic choice to accelerate the wound healing process.

Med Hypotheses 2020 Jan 3;134:109389. Epub 2019 Sep 3.

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The healing process of non-healing and full-thickness wounds is currently facing some serious challenges. In such ulcers, losing a large part of skin causes a chronic infection due to the entrance of various pathogens in the wound bed. Moreover, poor vascularization, uncontrolled inflammation, and delayed re-epithelialization increase the healing time in patients suffering from such wounds. In this light, tissue engineering provides a wide range of strategies using a variety of biomaterials, biofactors and stem cells to decrease the healing time and restore the function of the damaged site. A suitable wound healing agent should possess some critical parameters such as inducing re-epithelialization, anti-inflammatory and anti-bacterial properties, and angiogenic capability. The Lacto-n-Neotetraose (LNnT) with chemical formula C26H45NO21 is an oligosaccharide present in human milk and soluble antigens extracted from Schistosoma mansoni eggs. It is reported that LNnT induces type 2 immune response (Th2 immunity). Th2 immunity promotes re-epithelialization, angiogenesis and wound contraction by recruiting the cells which produce Th2-related cytokines. Moreover, LNnT shows some special characteristics such as angiogenic capability, anti-inflammatory, and anti-bacterial effects which can address the mentioned challenges in the treatment of non-healing and full-thickness wounds. Here, we hypothesize that utilizing LNnT is an appropriate biofactor which would improve the healing process in full-thickness and non-healing wounds.
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http://dx.doi.org/10.1016/j.mehy.2019.109389DOI Listing
January 2020

How preparation and preservation procedures affect the properties of amniotic membrane? How safe are the procedures?

Burns 2020 09 21;46(6):1254-1271. Epub 2019 Aug 21.

Chemical Injuries Research Center, Systems Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran; Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address:

Human amniotic membrane (AM) has been widely used for tissue engineering and regenerative medicine applications. AM has many favorable characteristics such as high biocompatibility, antibacterial activity, anti-scarring property, immunomodulatory effects, anti-cancer behavior and contains several growth factors that make it an excellent natural candidate for wound healing. To date, various methods have been developed to prepare, preserve, cross-link and sterilize the AM. These methods remarkably affect the morphological, physico-chemical and biological properties of AM. Optimization of an effective and safe method for preparation and preservation of AM for a specific application is critical. In this review, the isolation, different methods of preparation, preservation, cross-linking and sterilization as well as their effects on properties of AM are well discussed. For each section, at least one effective and safe protocol is described in detail.
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http://dx.doi.org/10.1016/j.burns.2019.07.005DOI Listing
September 2020

Crosstalk between chitosan and cell signaling pathways.

Cell Mol Life Sci 2019 Jul 27;76(14):2697-2718. Epub 2019 Apr 27.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

The field of tissue engineering (TE) experiences its most exciting time in the current decade. Recent progresses in TE have made it able to translate into clinical applications. To regenerate damaged tissues, TE uses biomaterial scaffolds to prepare a suitable backbone for tissue regeneration. It is well proven that the cell-biomaterial crosstalk impacts tremendously on cell biological activities such as differentiation, proliferation, migration, and others. Clarification of exact biological effects and mechanisms of a certain material on various cell types promises to have a profound impact on clinical applications of TE. Chitosan (CS) is one of the most commonly used biomaterials with many promising characteristics such as biocompatibility, antibacterial activity, biodegradability, and others. In this review, we discuss crosstalk between CS and various cell types to provide a roadmap for more effective applications of this polymer for future uses in tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1007/s00018-019-03107-3DOI Listing
July 2019

Antibody-drug conjugates (ADCs) for cancer therapy: Strategies, challenges, and successes.

J Cell Physiol 2019 05 27;234(5):5628-5642. Epub 2018 Nov 27.

Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody-drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.
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http://dx.doi.org/10.1002/jcp.27419DOI Listing
May 2019

Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients.

Amino Acids 2018 Nov 25;50(11):1617-1628. Epub 2018 Aug 25.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml and ≥ 4 mg ml for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml and ≥ 4 mg ml, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml and ≤ 32 μg ml, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial.
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http://dx.doi.org/10.1007/s00726-018-2638-zDOI Listing
November 2018

Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine.

Artif Cells Nanomed Biotechnol 2018 24;46(sup2):431-440. Epub 2018 Apr 24.

a Department of Pharmacology, School of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

One of the main goals of tissue engineering and regenerative medicine is to develop skin substitutes for treating deep dermal and full thickness wounds. In this regard, both scaffold and cell source have a fundamental role to achieve exactly the same histological and physiological analog of skin. Amnion epithelial and mesenchymal cells possess the characteristics of pluripotent stem cells which have the capability to differentiate into all three germ layers and can be obtained without any ethical concern. Amniotic cells also produce different growth factors, angio-modulatory cytokines, anti-bacterial peptides and a wide range of anti-inflammatory agents which eventually cause acceleration in wound healing. In addition, amniotic membrane matrix exhibits characteristics of an ideal scaffold and skin substitute through various types of extracellular proteins such as collagens, laminins and fibronectins which serve as an anchor for cell attachment and proliferation, a bed for cell delivery and a reservoir of drugs and growth factors involved in wound healing process. Recently, isolation of amniotic cells exosomes, surface modification and cross-linking approaches, construction of amnion based nanocomposites and impregnation of amnion with nanoparticles, construction of amnion hydrogel and micronizing process promoted its properties for tissue engineering. In this manuscript, the recent progress was reviewed which approve that amnion-derived cells and matrix have potential to be involved in skin substitutes; an enriched cell containing scaffold which has a great capability to be translated into the clinic.
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http://dx.doi.org/10.1080/21691401.2018.1458730DOI Listing
June 2019