Publications by authors named "Zahra Nozhat"

9 Publications

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Application of Bacterial Nanocellulose in the Cancer Drug Delivery: A Review.

Curr Pharm Des 2021 Apr 12. Epub 2021 Apr 12.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Bacterial nanocellulose (BNC) is one of the natural biopolymers with unique features, the most important of which are nontoxicity, biocompatibility, high tensile profile, nanofiber structure, and purity. The current review aimed to summarize the latest development in BNC-based biomaterials in cancer drug delivery. The original articles were found by searching key databases including PubMed, Scopus, and Web of Scientific and using key terms such as "bacterial nanocellulose OR bacterial cellulose OR BNC" AND "cancer OR carcinoma OR tumor". The obtained data were in a wide timeframe and the English language. Totally, 350 articles were found from the three main databases (i.e., 106, 251, and 173 articles from PubMed, Scopus, and the Web of Science, respectively). In general, 32 articles met the inclusion criteria after duplicate removal and screening according to the aim of the present review study. In this review study, different applications of the bacterial nanocellulose were considered for cancer drug delivery in addition to describing advanced methods that may be applied to improve therapeutic potency while reducing the adverse effects of chemodrugs by decreasing their dosages. The high ratio of the surface area-to-volume and easy modifications of their chemical components lead BNC potential use as an appropriate matrix structure for the binding and controlled release of various pharmaceutical agents, specifically for topical or transdermal administrations. In addition, BNC-based products regulate the release of hydrophobic and hydrophilic compounds, therefore, provide appropriate materials related to cancer drug delivery. However, undoubtedly, further developments of BNC-based products as cancer drug delivery systems require more extensive investigations.
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http://dx.doi.org/10.2174/1381612827666210412150445DOI Listing
April 2021

Antineoplastic Activity of an Old Natural Antidiabetic Biguanoid on the Human Thyroid Carcinoma Cell Line.

Anticancer Agents Med Chem 2021 Jan 17. Epub 2021 Jan 17.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran. Iran.

Background: In the last decades, metformin (Met), an herbal anti-diabetic medicine, has been proposed as an anti-cancer agent.

Objective: Thyroid cancers are the most common malignancy of the endocrine system. Therefore, the current study was performed to assess the effects of Met on cell proliferation and activation of the Phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid Carcinoma (MTC) cells. The effects of Met on the expression of REarranged during Transfection (RET) proto-oncogene were also investigated.

Methods: MTC cell line (TT) was treated with 0, 2.5, 5, 10, 20, 30, 40, 50, and 60 mM concentrations of Met for 24, 48, and 72h. The viability and apoptosis of the treated cells were measured by the 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) and Annexin V- Propidium Iodide (PI) assays. The expression level of PI3K, AKT, FOXO1, and RET genes was investigated by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and phosphorylation of their proteins was determined by the Enzyme-Linked Immunosorbent Assay (ELISA).

Results: Results showed that Met significantly decreased the viability of the MTC cells. Met also reduced the expression level of PI3K, AKT, and FOXO1 genes (P<0.05), whereas it elevated the expression level of RET proto-oncogene (P<0.05).

Conclusion: It seems that the Met has cytostatic effect on the TT cells. Our results showed that anti-tumoral effects of Met may be cell type-specific, and according to the induction of RET (as a proto-oncogene) and inhibition of FOXO1 (as a tumor suppressor gene), Met could not be an appropriate agent in treatment of MTC. The antineoplastic activity of Met has been confirmed against several malignancies in 'in vitro' and 'in vivo' studies. However, its molecular mechanisms in the treatment of different carcinomas particularly in thyroid cancers are not clearly understood and more studies are required to confirm its exact effect on the MTC.
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http://dx.doi.org/10.2174/1871520621666210118093532DOI Listing
January 2021

Different Methods for Cell Viability and Proliferation Assay: Essential Tools in Pharmaceutical Studies.

Anticancer Agents Med Chem 2020 Dec 30. Epub 2020 Dec 30.

Laboratory for Red Blood Cell Diagnostics, Sanquin, Amsterdam,. Netherlands.

Background And Objective: The ratio of live cells to total cells in a sample is a definition for cell viability or cell toxicity. The assessment of the viable cells plays a critical role in all processes of the cell culture workflows. Overall, they are used to evaluate the survival of cells and also to optimize culture or experimental conditions following treatment with different agents or compounds, like during a drug screen. In most cases, the measurement of cell viability is the primary purpose of the experiments, for example, in pharmaceutical studies to evaluate agents' toxicity.

Methods: A literature research was conducted on cell viability assays in MEDLINE (PubMed), Web of Science and Scopus.

Results: There is a wide range of cell viability assays and different parameters such as cost, speed, and complexity of a test effect to determine the choosing method. However each method has some advantages and disadvantages and none of them is not 100% perfect method.

Conclusion: Accordingly, it seems that the simultaneous utility of at least two assays will cover each other disadvantages to demonstrate the effects of different agents on different cell types. For instance, when one assay measures cell metabolic health, the other one checks cells permeability. Therefore by this strategy a researcher can report with more confidence the effective doses of the examined therapeutic agents.
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http://dx.doi.org/10.2174/1871520621999201230202614DOI Listing
December 2020

BRAF V600E mutation and microRNAs are helpful in distinguishing papillary thyroid malignant lesions: Tissues and fine needle aspiration cytology cases.

Life Sci 2019 Apr 16;223:166-173. Epub 2019 Mar 16.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran. Electronic address:

Aims: Mutations of BRAF oncogene are considered to contribute in the invasiveness and poor clinicopathologic features of papillary thyroid cancer (PTC). As a step towards understanding the underlying molecular mechanisms of this contribution, we aimed to examine the association of four microRNAs' (miR-222, -137, -214, -181b) levels with BRAFV600E and clinicopathological features in PTC tissues and fine needle aspiration (FNA) specimens.

Methods: In total, 56 PTC and 27 benign with multinodular goiter tissue samples, 95 FNA samples, and B-CPAP and HEK293 cell lines were examined. BRAFV600E mutation was examined in PTC tissues and FNA samples. Expression of microRNAs was assessed by real-time quantitative reverse transcription-PCR.

Key Findings: The frequency of BRAFV600E in PTC tissues and FNA samples "suspicious for PTC" was 41.1 and 36.8%, respectively. MiR-222, -137, -214, and -181b were significantly upregulated in PTC tumors (P < 0.05) and in B-CPAP cell line (P < 0.001). In FNA, the expressions of miR-222, -181b and -214 were significantly elevated in patients suspected for PTC (P < 0.05), while there was no significant difference in miR-137. After adjustment for age and sex, miR-181b was associated with an increased risk of bearing BRAFV600E mutation (OR: 1.27; 95% CI: 1.01-1.61; P = 0.045) and risk of lymphovascular invasion (OR: 1.66; 95% CI: 1.01-2.72; P = 0.045); miR-137 was associated with the risk of larger tumor size (OR: 1.31; 95% CI: 1.04-1.65; P = 0.022); miR-222 was related to increase in extracapsular invasion (OR: 1.28; 95% CI: 1.04-1.57; P = 0.018).

Significance: Upregulation of miR-222, -214 and -181b has been confirmed in PTC tumors, FNA samples and cell line. MiR-137 upregulation has been confirmed in PTC tumors and cell line, but not in FNA samples. MiR-222, -137 and -181b showed an association with the degree of malignancy in PTC tumors.
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http://dx.doi.org/10.1016/j.lfs.2019.03.034DOI Listing
April 2019

Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.

Daru 2018 Dec 21;26(2):93-103. Epub 2018 Sep 21.

Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The PI3K/AKT/FOXO signaling pathway plays an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore whether metformin could affect insulin-promoting cell growth by regulation of this pathway.

Material And Methods: Anaplastic thyroid cancer cells were treated with 0-60 mM metformin for 24, 48 and 72 h. Cell viability, morphology, apoptosis and migration were investigated by MTT assay, microscopy observation, AnexinV-PI and the wound healing assay, respectively. Expression levels of PI3K, AKT and FOXO1 were detected by RT-qPCR, and proteins phosphorylated levels were determined by ELISA.

Results: Metformin decreased cell viability and migration in a significant time-and dose-dependent manner, and induced apoptosis and morphological changes in the cells. RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P < 0.05). However, there was no significant change in the expression level of AKT following metformin treatment for C643 cell line (P > 0.05). ELISA results showed that metformin treatment had no significant effects on the phosphorylated levels of PI3K, AKT and FOXO1 (P > 0.05).

Conclusuion: The downregulation of FOXO1 was intensified by metformin, but no increase in cell viability was observed following FOXO1 downregulation by metformin. However, the exact molecular mechanism of metformin on inhibition of the PI3K/AKT pathway and subsequent decrease in cell viability remains unclear and further studies are required for its clarification.
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http://dx.doi.org/10.1007/s40199-018-0208-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279666PMC
December 2018

Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer?

Asian Pac J Cancer Prev 2016 ;17(S3):119-23

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences,Shahid Beheshti University of Medical Sciences, Tehran, IranE-mail:

Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, 29±13.9 years, 25 females, 29±14.5 years) and 45 control individuals (25 males, 23.1±11.6 years, 20 females, 31.5±14.4 years). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (P<0.01) . There was also a significant difference mean of Mst between females in control and MTC groups, but not for the males. Pearson correlation test showed no correlation between age and BMI with Mst serum levels. The findings of this study support the hypothesis that Mst serum levels may have a potential ability for early diagnosis of cachexia in MTC patients, especially in females.
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http://dx.doi.org/10.7314/apjcp.2016.17.s3.119DOI Listing
February 2017

Medullary thyroid carcinoma: a review on ethical considerations in treatment of children.

J Pediatr Endocrinol Metab 2016 Jun;29(6):633-9

Thyroid carcinoma is the most common malignancy of the endocrine system and it accounts approximately 1%-3% of all human cancers. Among the three subtypes of thyroid cancers, medullary thyroid carcinoma (MTC) is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN2A), MEN type 2B (MEN2B) and familial medullary thyroid carcinoma (FMTC). Generally, MTC accounts for up to 10% of all types of thyroid cancers. It is one of the aggressive forms of thyroid carcinoma which is manifested in childhood ages more than adults, and it comprises about 17% of all pediatric thyroid cancer. Like the other cancers, prevention of MTC is easier than its cure. In the recent decades (from 1993) the diagnosis of asymptomatic child carrying RET mutations in the affected families by MTC, has been provided by genetic screening, and prophylactic thyroidectomy is an efficacy therapeutic procedure. On the one hand, according to near the complete penetrance of the disease and its onset in the early years of life, it is required to accelerate the protection of at-risk children with relative affected by MTC and on the other hand, there are several obstructions to MTC treatment including: 1) the proband's refusal to disclose the RET mutation genetic testing results, 2) children's vulnerability because of their inability to participate in the informed consent, and 3) the existence of conflict between physicians and children's guardian. In this review article, the recommendations and ethical issues of MTC treatment in asymptomatic and at-risk children have been summarized.
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http://dx.doi.org/10.1515/jpem-2015-0309DOI Listing
June 2016

Thyroid Cancer Epidemic: A Peril or an Alarm?

Int J Endocrinol Metab 2015 Oct 10;13(4):e28491. Epub 2015 Oct 10.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.

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http://dx.doi.org/10.5812/ijem.28491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659334PMC
October 2015

PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas.

Mol Diagn Ther 2016 Feb;20(1):13-26

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Thyroid malignancies are the most common endocrine system carcinomas, with four histopathological forms. The phosphoinositide 3-kinase-protein kinase B/AKT (PI3K-PKB/AKT) pathway is one of the most critical molecular signaling pathways implicated in key cellular processes. Its continuous activation by several aberrant receptor tyrosine kinases (RTKs) and genetic mutations in its downstream effectors result in high cell proliferation in a broad number of cancers, including thyroid carcinomas. In this review article, the role of different signaling pathways of PI3K/AKT in thyroid cancers, with the emphasis on the PI3K/AKT/mammalian target of rapamycin (mTOR), PI3K/AKT/forkhead box O (FOXO) and PI3K/AKT/phosphatase and tensin homolog deleted on chromosome ten (PTEN) pathways, and various therapeutic strategies targeting these pathways have been summarized. In most of the in vitro studies, agents inhibiting mTOR in monotherapy or in combination with chemotherapy for thyroid malignancies have been introduced as promising anticancer therapies. FOXOs and PTEN are two outstanding downstream targets of the PI3K/AKT pathway. At the present time, no study has been undertaken to consider thyroid cancer treatment via FOXOs and PTEN targeting. According to the critical role of these proteins in cell cycle arrest, it seems that a treatment strategy based on the combination of FOXOs or PTEN activity induction with PI3K/AKT downstream mediators (e.g., mTOR) inhibition will be beneficial and promising in thyroid cancer treatment.
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http://dx.doi.org/10.1007/s40291-015-0175-yDOI Listing
February 2016