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1. Optimization of molecularly targeted MRI in the brain: empirical comparison of sequences and particles

Author

Zarghami N, Khrapitchev AA, Perez-Balderas F, Sarmiento Soto M, Larkin JR, Bau L, and Sibson NR

Subjects
Molecular imaging, Preclinical MRI, VCAM-MPIO, VCAM-USPIO, Multi gradient echo, bSSFP, Medicine (General), R5-920
Abstract

Niloufar Zarghami,1 Alexandre A Khrapitchev,1 Francisco Perez-Balderas,1 Manuel Sarmiento Soto,1 James R Larkin,1 Luca Bau,2 Nicola R Sibson1 1Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK; 2Institute of Biomedical Engineering, Department of Engineering Sciences, University of Oxford, Oxford, UK Background: Molecular MRI is an evolving field of research with strong translational potential. Selection of the appropriate MRI sequence, field strength and contrast agent depend largely on the application. The primary aims of the current study were to: 1) assess the sensitivity of different MRI sequences for detection of iron oxide particles in mouse brain; 2) determine the effect of magnetic field strength on detection of iron oxide particles in vivo; and 3) compare the sensitivity of targeted microparticles of iron oxide (MPIO) or ultra-small superparamagnetic iron oxide (USPIO) for detection of vascular cell adhesion molecule-1 (VCAM-1) in vivo. Methods: Mice were injected intrastriatally with interleukin 1β to induce VCAM-1 expression on the cerebral vasculature. Subsequently, animals were injected intravenously with either VCAM-MPIO or VCAM-USPIO and imaged 1 or 13 hours post-injection, respectively. MRI was performed at 4.7, 7.0, or 9.4 T, using three different T2*-weighted sequences: single gradient echo 3D (GE3D), multi-gradient echo 3D (MGE3D) and balanced steady-state free precession 3D (bSSFP3D). Results: MGE3D yielded the highest signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the detection of iron oxide particles. All sequences showed a significant increase in SNR and CNR from 4.7 to 7.0 T, but no further improvement at 9.4 T. However, whilst targeted MPIO enabled sensitive detection of VCAM-1 expression on the cerebral vasculature, the long half-life (16.5 h vs 1.2 min) and lower relaxivity per particle (1.29×10–14 vs 1.18×10–9 Hz L/particle) of USPIO vs. MPIO rendered them impractical for molecular MRI. Conclusion: These findings demonstrate clear advantages of MPIO compared to USPIO for molecularly-targeted MRI, and indicate that the MGE3D sequence is optimal for MPIO detection. Moreover, higher field strengths (7.0/9.4 T) showed enhanced sensitivity over lower field strengths (4.7 T). With the development of biodegradable MPIO, these agents hold promise for clinical translation. Keywords: molecular imaging, preclinical MRI, VCAM-MPIO, VCAM-USPIO, multi gradient echo, bSSFP

Published
2018

2. Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin [Retraction]

Author

Akbarzadeh A, Zarghami N, Mikaeili H, Asgari D, Goganian AM, Khiabani HK, Samiei M, and Davaran S

Subjects
Medical technology, R855-855.5, Chemical technology, TP1-1185
Abstract

Akbarzadeh A, Zarghami N, Mikaeili H, et al. Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin. Nanotechnol Sci Appl. 2012;5:13–25. The Editor-in-Chief and Publisher of Nanotechnology, Science and Applications wish to retract the published article. Concerns were raised about the level of similarity between the published article and another article published by the same authors in the International Journal of Nanomedicine titled ‘Preparation and in vitro evaluation of doxorubicin loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers’ (http://dx. doi.org/10.2147/IJN.S24326). Following a review, it was determined the level of text matching between the two articles was unacceptable. In addition, it was found there was an unacceptable level of image duplication between the same two articles and the findings and conclusions in the present study were no longer supported. The affected figures within the present article are: ● Figure 2 is the same as Figure 1 in the International Journal of Nanomedicine article● Figure 3 is the same as Figure 3C in the International Journal of Nanomedicine article● The MTT assay results in Figure 5 are the same as those presented in the MTT assay results in Figure 6 of the International Journal of Nanomedicine article● Figure 6B is the same as Figure 7D in the International Journal of Nanomedicine article● Figure 7A is the same as Figure 8 in the International Journal of Nanomedicine article● Figure 8A is the same as Figure 9A in the International Journal of Nanomedicine article● Figure 9A is the same as Figure 12A in the International Journal of Nanomedicine article● The optical images in Figure 12A, B and C are the same as those presented in the optical images in Figure 15A, B and C of the International Journal of Nanomedicine article Our decision-making was informed by COPE’s retraction guidelines. The authors cooperated throughout the process and agree with the decision to retract. The authors wish to apologize for this error. This retraction relates to this paper

Published
2019

3. Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin

Author

Akbarzadeh A, Zarghami N, Mikaeili H, Asgari D, Goganian AM, Khiabani HK, Samiei M, and Davaran S

Subjects
Medical technology, R855-855.5, Chemical technology, TP1-1185
Abstract

Abolfazl Akbarzadeh1, Nosratollah Zarghami2, Haleh Mikaeili3, Davoud Asgari4, Amir Mohammad Goganian5, Hanie Khaksar Khiabani5, Mohammad Samiei6, Soodabeh Davaran31Department of Medicinal Chemistry, Tabriz University of Medical Sciences, 2Department of Clinical Biochemistry and Laboratory Medicine, Division of Medical Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, 3Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, 4Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, 5Department of Organic Chemistry, Faculty of Chemistry, University of Tabriz, 6Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, IranAbstract: Poly (N-isopropylacrylamide-methyl methacrylic acid, PNIPAAm-MAA)-grafted magnetic nanoparticles were synthesized using silane-coated magnetic nanoparticles as a template for radical polymerization of N-isopropylacrylamide and methacrylic acid. Properties of these nanoparticles, such as size, drug-loading efficiency, and drug release kinetics, were evaluated in vitro for targeted and controlled drug delivery. The resulting nanoparticles had a diameter of 100 nm and a doxorubicin-loading efficiency of 75%, significantly higher doxorubicin release at 40°C compared with 37°C, and pH 5.8 compared with pH 7.4, demonstrating their temperature and pH sensitivity, respectively. In addition, the particles were characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. In vitro cytotoxicity testing showed that the PNIPAAm-MAA-coated magnetic nanoparticles had no cytotoxicity and were biocompatible, indicating their potential for biomedical application.Keywords: magnetic nanoparticles, drug loading, doxorubicin release, biocompatibility

Published
2012

4. Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers

Author

Akbarzadeh A, Mikaeili H, Zarghami N, Mohammad R, Barkhordari A, and Davaran S

Subjects
Medicine (General), R5-920
Abstract

Abolfazl Akbarzadeh1, Haleh Mikaeili2, Nosratollah Zarghami3, Rahmati Mohammad3, Amin Barkhordari3, Soodabeh Davaran21Drug Applied Research Center, 2Tuberculosis and Lung Disease Research Center of Tabriz, 3Department of Clinical Biochemistry and Laboratory Medicine, Division of Medical Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranBackground: Superparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxorubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet.Methods: A series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG2000, PEG3000, and PEG4000) as an initiator. The bulk properties of these copolymers were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry.Results: The doxorubicin encapsulation amount was reduced for PLGA:PEG2000 and PLGA:PEG3000 triblock copolymers, but increased to a great extent for PLGA:PEG4000 triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe3O4 magnetic nanoparticles modified with PLGA:PEG2000, PLGA:PEG3000, and PLGA:PEG4000 copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe3O4-PLGA:PEG4000 magnetic nanoparticles had no cytotoxicity and were biocompatible.Conclusion: There is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer.Keywords: superparamagnetic iron oxide nanoparticles, triblock copolymer, doxorubicin encapsulation, water uptake, drug encapsulation efficiency

Published
2012

5. Relationship between vitreous and serum vascular endothelial growth factor levels, control of diabetes and microalbuminuria in proliferative diabetic retinopathy

Author

Bahariv, N, Zarghami N, Panahi F, Dokht Ghafari M Y, Mahdavi Fard A, and Mohajeri A

Subjects
Ophthalmology, RE1-994
Abstract

Nader Baharivand1, Nosratollah Zarghami2, Farid Panahi3, Yazdan Dokht Ghafari M3, Ali Mahdavi Fard1, Abbas Mohajeri21Department of Ophthalmology, Nikookari Eye Hospital, 2Department of Clinical Biochemistry and Radiopharmacy, Drug Applied Research Center, 3Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranBackground: Diabetic retinopathy is a serious microvascular disorder of the retina. Vascular endothelial growth factor (VEGF) expression, induced by high glucose levels and hypoxia, is a main feature in retinopathy. The aim of this study was to evaluate the relationship between vitreous and serum VEGF levels and control of diabetes and microalbuminuria in patients with proliferative diabetic retinopathy.Methods: Sixty-five patients were enrolled in this case-control study, comprising 30 patients with proliferative diabetic retinopathy (cases) and 35 patients with nonproliferative diabetic retinopathy (controls). The vitreous VEGF level was compared with the serum VEGF level in both groups. Glycosylated hemoglobin (HbA1c), microalbuminuria, serum creatinine, and stage of nephropathy and retinopathy were also measured in patients with proliferative diabetic retinopathy, and the relationship between these parameters and serum and vitreous VEGF levels was investigated.Results: Mean vitreous and serum VEGF levels were significantly higher in cases compared with controls (P = 0.001, P = 0.011, respectively). There was also a significant correlation between vitreous and serum VEGF levels (P = 0.012, r = 0.453). VEGF levels in patients with well controlled blood glucose (P = 0.039), on drug treatment (P = 0.045) and at an early stage of nephropathy (P = 0.042) were significantly lower. There was a significant correlation between VEGF and albumin to creatinine ratio (P = 0.017, r = 0.432).Conclusion: Serum and vitreous VEGF levels was significantly lower in patients on oral therapy, in those with well controlled glycemia, and in those with early-stage retinopathy. Administration of anti-VEGF had a good effect in reducing the progression of proliferative diabetic retinopathy.Keywords: proliferative diabetic retinopathy, vascular endothelial growth factor, vitreous body

Published
2012

7. Novel molecular MRI approaches to the detection of brain metastasis

Author

Zarghami, N, Vallis, K, Blamire, A, and Sibson, N

Abstract

Secondary brain cancer (brain metastasis) is a leading cause of cancer morbidity and mortality. As treatments for primary tumours and systemic metastatic disease improve, the significance of brain metastasis as a cause of death increases. The poor survival of patients with brain metastasis is partly attributed to the unique microenvironment of the brain, includes the blood-brain barrier (BBB), which limits penetration of systemics cancer therapies and imaging contrast agents, and partly to the late stage of diagnosis. Current diagnosis relies on breakdown of the BBB, which only occurs at later stages of metastasis progression and, thus, delaying the introduction of potential treatments. To address this critical issue, development of novel molecular magnetic resonance imaging (MRI) contrast agents for the detection of brain metastasis at the early stages of formation was the overall focus of this thesis. Inflammation is a hallmark of many neurological disorders, and expression of cell adhesion molecules on blood vessels is a key component of this process. Brain endothelial activation can readily be targeted by iron oxide particles in vivo and unmasked using routine MRI acquisition methods. A number of different types of iron oxide particles, MRI sequences and magnetic field strengths have been used previously for visualising this endothelial activation. Hence, in this thesis, the initial aim was to optimise each of these parameters to further improve molecular MRI in mouse brain. Endothelial activation is also an early event in the development of brain metastasis. Two adhesion molecules, activated leukocyte cell adhesion molecule (ALCAM) and E selectin, were assessed in brain metastasis models from three primary tumours (breast, melanoma and lung) as potential biomarkers for detection of brain micrometastases in the preclinical models. Iron oxide based microparticles against these surrogate biomarkers of brain metastases were developed, validated and applied in vivo. The results of this work demonstrated that targeting both ALCAM and E selectin can reveal brain metastases at the microscopic level, and before conventional imaging methods. The advances in our ability to detect early brain metastatic stages using molecular MRI, and the presented contrast agents in this body of work is likely to yield substantial improvements in patient survival.

Published
2022

9. Design and Development of Modified mRNA Encoding Core Antigen of Hepatitis C Virus: a Possible Application in Vaccine Production

Author

Sharifnia, Z., Mojgan Bandehpour, Kazemi, B., and Zarghami, N.

Subjects
Viral Hepatitis Vaccines, Vaccines, Transcription, Genetic, Viral Core Proteins, Full Length, Messenger, Green Fluorescent Proteins, Dendritic Cells, Hepacivirus, Hepatitis C, Monocytes, RNA, Humans, Nucleic Acid Conformation, Thermodynamics, RNA, Messenger, Plasmids
Abstract

Background: Hepatitis C virus (HCV) is a blood-borne pathogen, resulting in liver cirrhosis and liver cancer. Despite of many efforts in development of treatments for HCV, no vaccine has been licensed yet. The purpose of this study was to design and prepare a specific mRNA, without 5’ cap and poly (A) tail transcribed in vitro capable of coding core protein and also to determine its functionality. Methods: Candidate mRNA was prepared by in vitro transcription of the designed construct consisting of 5’ and 3’ untranslated regions of heat shock proteins 70 (hsp70) mRNA, T7 promoter, internal ribosome entry site (IRES) sequences of eIF4G related to human dendritic cells (DCs), and the Core gene of HCV. To design the modified mRNA, the 5’ cap and poly (A) tail structures were not considered. DCs were transfected by in vitro-transcribed messenger RNA (IVT-mRNA) and the expressions of green fluorescent protein (GFP), and Core genes were determined by microscopic examination and Western blotting assay. Results: Cell transfection results showed that despite the absence of 5’ cap and poly (A) tail, the structure of the mRNA was stable. Moreover, the successful expressions of GFP and Core genes were achieved. Conclusion: Our findings indicated the effectiveness of a designed IVT-mRNA harboring the Core gene of HCV in transfecting and expressing the antigens in DCs. Considering the simple and efficient protocol for the preparation of this IVT-mRNA and its effectiveness in expressing the gene that it carries, this IVT-mRNA could be suitable for development of an RNA vaccine against HCV.

Published
2019

11. Visfatin effects on telomerase gene expression in AGS gastric cancer cell line

Author

Mohammadi, M., Zarghami, N., Hedayati, M., Ghaemmaghami, S., Yamchi, R., and Mohaddes, M.

Subjects
Stomach cancer -- Genetic aspects -- Development and progression, Transferases -- Health aspects, Telomerase -- Health aspects, Gene expression -- Health aspects, Health
Abstract

Byline: M. Mohammadi, N. Zarghami, M. Hedayati, S. Ghaemmaghami, R. Yamchi, M. Mohaddes Aim: The aim of this study was to assess visfatin expression and its effect on human telomerase [...]

Published
2015

15. Theoretical and experimental studies on the structure-antioxidant activity relationship of synthetic 4-methylcoumarins

Author

Barzegar A, Davari MD, Chaparzadeh N, Zarghami N, Pedersen JZ, LSaso L, Moosavi Movahedi AA, INCERPI, Sandra, Barzegar, A, Davari, Md, Chaparzadeh, N, Zarghami, N, Pedersen, Jz, Incerpi, Sandra, Lsaso, L, and Moosavi Movahedi, Aa

Subjects
reactive oxygen specie, antioxidant, coumarin
Abstract

The development of antioxidants as useful drugs for the treatment of neurodegenerative diseases such as Alzheimer's is extremely challenging in medicinal chemistry. Coumarins have attracted great attention as possible therapeutic tools against oxygen radicals in human degenerative diseases. In order to establish the possible structure-antioxidant activity relationship, a series of twenty four 4-methylcoumarin derivatives were examined by employing reducing power measurements, and comparison with bond dissociation enthalpy and ionization potential calculations. Based on the reducing potency of 4-methylcoumarin derivatives with respect to trolox, these compounds were classified into five groups as “most active”, “more active”, “moderately active”, “less active” and “inactive” derivatives. The presence of hydroxyl groups is an essential requirement for the activity, and substitution of hydroxyl groups by methoxy groups leads to non-active derivatives. The results revealed that dihydroxyl groups in the ortho position show a better antioxidant activity with respect to dihydroxyl groups in the meta position. This is ascribed to the ability to construct more stable 4-methylcoumarin radical intermediates by rearrangement of intra-molecular hydrogen bonding. Our findings indicate that other important factors to enhance the antioxidant activity of coumarins are the number of hydroxyl groups, the presence of ester substitutions and a thiono functional group on the pyrone ring. However, bond dissociation enthalpy and ionization potential calculations alone are not sufficient to identify the best antioxidant structures. As a result, chemical and functional properties of molecules such as 4-methylcoumarins should be examined as a whole entity, considering all substitutions versus a single substitution to design functional compounds with good antioxidant activity.

Published
2011

21. Identification of over producer strain of endo-ß-1,4-glucanase in Aspergillus Species: Characterization of crude carboxymethyl cellulase

Author

Onsori, H., mohammadreza zamani, Motallebi, M., and Zarghami, N.

Subjects
Aspergillus sp., Endo-β-1, 4-glucanase, CMCase, SDS-PAGE, PCR
Abstract

Cellulases are a group of hydrolytic enzymes capable of degrading cellulose to smaller sugar components like glucose units. These enzymes are produced by fungi and bacteria. The aim of this research was to identify a Aspergillus species with over production of endo-β-1,4-glucanase. Properties of endo-β-1,4-glucanase/carboxymethylcellulase (CMCase) from a culture filtrate of the Aspergillus sp. was also studied. Aspergillus sp. (R4) was selected as over producer of endo-β-1,4-glucanase among 13 different species. SDS-PAGE activity staining with 1% Congo Red solution revealed three protein bands showing cellulolytic activity. The molecular weights of these proteins were estimated to be approximately 18.5, 23 and 28 kD. Also, conservative region of endo-β-1,4-glucanase coding gene was studied by polymerase chain reaction (PCR). Amplified fragments with 1204 bp and 399 bp were confirmed by restriction pattern with HindII and PstI enzymes. Key Words: Aspergillus sp., Endo-β-1, 4-glucanase, CMCase, SDS-PAGE, PCR. African Journal of Biotechnology Vol.4(1) 2005: 26-30

Published
2005

33. Detection of Telomerase Activity in Breast Tissue of Breast Cancer Patients and Healthy Individuals by the TRAP Assay.

Author

Asadi, J. and Zarghami, N.

Abstract

Background and Objective: Breast cancer is the most common cancer in women. Telomerase enzyme is one of the major factors causing the development and proliferation of immortal cells such as cancer cell. The aim of this study was to evaluate telomerase activity in breast tissues of breast cancer patients and healthy people. Material and Methods: In this descriptive study, the samples from 32 patients with malignant tumors and from 24 with benign tumors or healthy individuals were obtained .To assess the relative activity of telomerase in the samples, TRAP assay (PCR-ELISA) was used. Results: The frequency of telomerase activity was 93.75% in patients and 8% in healthy people. Conclusion: The results indicate that the relative activity of telomerase in tumor tissues measured by TRAP assay could be a suitable biomarker for identifying the breast cancer tissue. [ABSTRACT FROM AUTHOR]

Published
2014

47. Significance of microRNA targeted estrogen receptor in male fertility

Author

alireza abhari, Zarghami, N., Shahnazi, V., Barzegar, A., Farzadi, L., Karami, H., Vahed, S. Z., and Nouri, M.

Subjects
Has-mir-100, Fertility, lcsh:R, lcsh:Medicine, Has-let-7b, Original Article, MicroRNA
Abstract

Objective(s): Estrogen receptor-alpha (ERα) mediates estrogen action in regulation of different levels of the hypothalamic-pituitary-testis axis. It has a key role in spermatogenesis. Estrogen receptor alpha knock-out (ER koα) male mice were infertile and severe impairment in spermatogenesis and seminiferous tubules was observed. Recently, it has been reported that microRNA (miRNA) mir-100 and let-7b were predicted to target ERα gene. MiRNA are small, endogenous, single stranded RNA molecules that regulate gene expression and have been implicated in various disease states. It has been proved that some miRNAs expression is tissue- and disease-specific, giving potential for identifying miRNAs as a diagnostic tool. Materials and Methods: In this study, the change in the expression levels of mir-100, let-7b and ERα expression levels were evaluated in oligospermic infertile patients (n=43) compared to control fertile subjects (n=43). After washing and separating sperms, total RNA was isolated and then cDNA was synthesized. The expression levels of mir-100 and let-7b and ERα were evaluated by real time PCR. Results: Mir-100, let-7b levels were significantly higher than those in control group (P=0.008 and P=0.009, respectively). We have found that, ERα level was significantly decreased in comparison with normal group (P< 0.0001). Conclusion: Changes in mir-100, let-7b and ERα expression levels in oligospermic patients may be associated with the susceptibility and progression of infertility. The results of this study indicate that miRNA can have a key role in spermatogenesis and might have a diagnostic and prognostic value in men infertility.

50. Association between steroid hormone receptors and PSA gene expression in breast cancer cell lines

Author

Zarghami, N., Onsori, H., and behrang alani

Subjects
PSA, steroid hormone receptor, prostate cancer, breast cancer
Abstract

The prostate specific antigen (PSA) gene is a member of the human kallikrein gene family and is known that to be tightly regulated by androgens in the male prostate The presence of PSA is stronglyassociated with presence of steroid hormone receptors. The aim of this research was to show differential expression and association between steroid hormone receptors and PSA gene expression in breast cancer cell lines. The cell lines investigated were steroid receptor-negative breast carcinoma cell lines BT-20 and HBT-100 and the steroid hormone receptor-positive breast carcinoma cell lines BT- 474, ZR-75-1, MDA-MB-453 and MFM-233. Others include BG-1 (ovarian), MFE-296 (endometrium), HBT-161 (ovarian), HBT-173 (ovarian), A-427 (lung), SK-MES-1(lung), NCI-H460(lung),MIA PaCa (pancreas), and Colo320 (Colon) cell lines. All cell lines were cultured as confluent and then harvested. Stimulationtest was carried out using steroid compound. The concentration of estrogen receptor (ER) and progesterone receptor (PR) in all tumor cell lines were measured with the abbot enzyme immunoassay kit. Among cell lines tested, only steroid receptor positive cells were able to produce PSA at the protein and the mRNA level in response to stimulatory effects of steroid hormones. Our data suggest that the expression of the PSA gene in different cancer cell lines may depends on the presence of steroidhormone receptors.

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