Publications by authors named "Mehdi Dehghani"

62 Publications

The effects of aerobic training, resistance training, combined training, and healthy eating recommendations on lipid profile and body mass index in overweight and obese children and adolescents: A randomized clinical trial.

ARYA Atheroscler 2020 Sep;16(5):226-234

Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: The aim of this study was to evaluate the effects of 8 weeks of aerobic training, resistance training (RT), combined training, and nutritional recommendations on lipid profile and body mass index (BMI) in obese and overweight children and adolescents.

Methods: This randomized, clinical trial was conducted on 120 children and adolescents (10-19 years of age) with overweight and obesity. Participants were divided into 4 groups, the 3 intervention groups of high-intensity interval training (HIIT), RT, and combined training, and 1 non-exercising control group with healthy eating recommendations. We considered 24 sessions of training during 8 weeks for the intervention groups. The participants' anthropometric indices and lipid profile were assessed before and after the intervention.

Results: There were no significant differences between the groups in terms of anthropometric indices and lipid profiles before the intervention. After the intervention, there was a significant difference between the groups in terms of high-density lipoprotein (HDL) level; the control group (37.70 ± 9.45) and the HIIT group (43.65 ± 9.09) displayed the lowest and highest mean, respectively (P = 0.040). Comparison of physical variables and blood lipid profiles before and after the intervention showed a significant difference in waist circumference (P = 0.030), hip circumference (P ≤ 0.001), and HDL level (P = 0.040) in RT, HIIT, combined, and control groups.

Conclusion: These results demonstrate that the combined training program and HIIT program with nutritional recommendations in overweight and obese children and adolescents were more effective in reducing BMI and hip circumference, respectively.
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http://dx.doi.org/10.22122/arya.v16i5.1990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034757PMC
September 2020

Economic Burden of Colorectal Cancer: A Case of Fars, Iran.

Cancer Control 2021 Jan-Dec;28:10732748211009952

Health Human Resources Research Center, School of Management and Medical Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Among cancers, colorectal cancer is the third most common cancer in the world and the fourth leading cause of cancer deaths worldwide. Some studies have shown that the incidence of colorectal cancer is increasing in Iran and in Fars province. The present study aimed to determine the economic burden of colorectal cancer in patients referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences in 2019 from the patients' perspective. This is a partial economic evaluation and a cost-of-illness study conducted cross-sectionally in 2019. All the patients with colorectal cancer who had been referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences, and had medical records were studied through the census method (N = 96). A researcher-made data collection form was used to collect the cost data. The prevalence-based and bottom-up approaches were also used in this study. The human capital approach was applied to calculate indirect costs. The mean annual cost per patient with colorectal cancer in the present study was $10930.98 purchasing power parity (PPP) (equivalent to 5745.29 USD), the main part of which was the medical direct costs (74.86%). Also, among the medical direct costs per patient, the highest were those of surgeries (41.7%). In addition, the mean annual cost per patient with colorectal cancer in the country was $ 116917762 PPP (equivalent to 61451621.84 USD) in 2019. Regarding the considerable economic burden of colorectal cancer and in order to reduce the costs, these suggestions can be made: increasing the number of specialized beds through the cooperation of health donors, establishing free or low-cost accommodation centers for patients and their companions near the medical centers, using the Internet and cyberspace technologies to follow up the treatment of patients, and increasing insurance coverage and government drug subsidies on drug purchase.
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http://dx.doi.org/10.1177/10732748211009952DOI Listing
April 2021

The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL).

Cancer Immunol Immunother 2021 Mar 15. Epub 2021 Mar 15.

Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

For many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4 T cell subsets like CD4CD25FOXP3 regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4CD25FOXP3 Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se-) consumption) with diffuse large B-cell lymphoma (DLBCL) subtype at stable remission. The change in the frequency of Tregs and expression of immune checkpoint receptors including CTLA-4, LAG-3, TIM-3, and PD-L1 genes were evaluated after 3 months in both groups using flow cytometry and SYBR Green Real-time PCR method, respectively. The results showed that the frequency of CD4CD25FOXP3 Tregs and expression of immune checkpoint receptors did not significantly change after 3-month Se consumption in DLBCL patients. However, alteration in the frequency of CD4CD25FOXP3 Treg subsets was positively correlated with change in CTLA-4, LAG-3, and TIM-3 expression in the Se+ group. Three-month Se supplementation did not prevent relapse in Se+ group. Taken together, Se supplementation alone did not affect the frequency of CD4CD25FOXP3 Tregs, expression of checkpoint receptors, and prevention of relapse in DLBCL patients at stable remission phase but might influence the functional properties of other Treg subsets like CD4CD25FOXP3 Tregs.
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http://dx.doi.org/10.1007/s00262-021-02889-5DOI Listing
March 2021

Use of Nanosphere Self-Assembly to Pattern Nanoporous Membranes for the Study of Extracellular Vesicles.

Nanoscale Adv 2020 Oct 12;2(10):4427-4436. Epub 2020 May 12.

Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, USA.

Nanoscale biocomponents naturally released by cells, such as extracellular vesicles (EVs), have recently gained interest due to their therapeutic and diagnostic potential. Membrane based isolation and co-culture systems have been utilized in an effort to study EVs and their effects. Nevertheless, improved platforms for the study of small EVs are still needed. Suitable membranes, for isolation and co-culture systems, require pore sizes to reach into the nanoscale. These pore sizes cannot be achieved through traditional lithographic techniques and conventional thick nanoporous membranes commonly exhibit low permeability. Here we utilized nanospheres, similar in size and shape to the targeted small EVs, as patterning features for the fabrication of freestanding SiN membranes (120 nm thick) released in minutes through a sacrificial ZnO layer. We evaluated the feasibility of separating subpopulation of EVs based on size using these membranes. The membrane used here showed an effective size cut-off of 300 nm with the majority of the EVs ≤200 nm. This work provides a convenient platform with great potential for studying subpopulations of EVs.
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http://dx.doi.org/10.1039/D0NA00142BDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943038PMC
October 2020

Fluorescent labeling of extracellular vesicles.

Methods Enzymol 2020 29;645:15-42. Epub 2020 Sep 29.

Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, NY, United States; Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, United States. Electronic address:

Fluorescent labeling of extracellular vesicles (EVs) enables studying their uptake and influence on individual cells, biodistribution as well as facilitates their characterization using high-resolution flow cytometry at a single EV level. Here we describe the importance of fluorescent labeling, the available fluorescent dyes and labeling approaches, the characteristics of an ideal dye, and the available techniques for post-labeling purification. We discuss the importance of preserving the size of EVs for uptake, biodistribution, and characterization studies and focus on the effect of common lipophilic PKH and luminal CFSE dyes on the size of EVs. Lastly, we present an example protocol for luminal labeling of EVs and characterization of the effect of labeling on the size of EVs using nanoparticles tracking analysis (NTA).
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http://dx.doi.org/10.1016/bs.mie.2020.09.002DOI Listing
September 2020

Catastrophic retroperitoneal hemorrhage in COVID-19 patients under anticoagulant prophylaxis.

Urol Case Rep 2021 May 13;36:101568. Epub 2021 Jan 13.

Department of Urology, School of Medicine, Al-Zahra Hospital, Isfahan University of Medical Sciences, Iran.

COVID-19 patients are at high risk for both capillary micro thrombi and large vessel thrombosis. Anticoagulant administration in COVID-19 patients, especially in ICU setting, is recommended by some researchers. However, clinical guidelines don't yet recommend anticoagulation therapies in therapeutic doses in these patients. In this article, we try to introduce a less known complication of heparin application in COVID-19 patients. Retroperitoneal hemorrhage when involves the psoas muscle might be deadly because of the large volume of bleeding before causing any significant alarm. It is very important to be careful in diagnosing and managing this complication.
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http://dx.doi.org/10.1016/j.eucr.2021.101568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829136PMC
May 2021

An Emerging Fluorescence-Based Technique for Quantification and Protein Profiling of Extracellular Vesicles.

SLAS Technol 2021 Apr 13;26(2):189-199. Epub 2020 Nov 13.

Sartorius Corporate Research, Sartorius (Smart Labs), Boston, MA, USA.

Robust and well-established techniques for the quantification and characterization of extracellular vesicles (EVs) are a crucial need for the utilization of EVs as potential diagnostic and therapeutic tools. Current bulk analysis techniques such as proteomics and Western blot suffer from low resolution in the detection of small changes in target marker expression levels, exemplified by the heterogeneity of EVs. Microscopy-based techniques can provide valuable information from individual EVs; however, they are time-consuming and statistically less powerful than other techniques. Flow cytometry has been successfully employed for the quantification and characterization of individual EVs within larger populations. However, traditional flow cytometry is not highly suited for the examination of smaller, submicron particles. Here we demonstrate the accurate and precise quantification of nanoparticles such as EVs using the Virus Counter 3100 (VC3100) platform, a fluorescence-based technique that uses the principles of flow cytometry with critical enhancements to enable the effective detection of smaller particles. This approach can detect nanoparticles precisely with no evidence of inaccurate concentration measurement from masking effects associated with traditional nanoparticle tracking analysis (NTA). Fluorescently labeled EVs from different sources were successfully quantified using the VC3100 without a postlabeling washing step. Moreover, protein profiling and characterization of individual EVs were achieved and have been shown to determine the expression level of target protein markers.
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http://dx.doi.org/10.1177/2472630320970458DOI Listing
April 2021

Higher Peripheral Blood IFN-γ-/IL-4+ Th2 Lymphocytes Are Associated with Lower Rate of Relapse in Patients with Lymphoma.

Immunol Invest 2020 Nov 5:1-12. Epub 2020 Nov 5.

Hematology Research Center, Shiraz University of Medical Sciences , Shiraz, Iran.

Background: The role of T-helper lymphocytes especially T helper 2 (Th2) subsets in lymphoid malignancies is debatable and unknown.

Methods: Herein, we evaluated the polarization of the IFN-γ/IL-4 Th1 and IFN-γ/IL-4 Th2 lymphocytes in 95 lymphoma patients including 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma patients (DLBCL) at different disease phases and its correlation with the clinical outcomes of patients using flow cytometry method.

Results: The proportion of IFN-γ/IL-4 Th1 lymphocytes was significantly higher in cHL patients at remission compared to the newly diagnosed ones. Both cHL and DLBCL patients at remission phase had significantly more IFN-γ/IL-4 Th2 lymphocytes than those patients at relapse/refractory phase as well as newly diagnosed ones. Despite having higher frequency of IFN-γ/IL-4 Th1 lymphocytes, the mean fluorescent intensity (MFI) of IFN-γ was lower in relapsed cHL patients, in those with high-risk IPI score, performance status (PS) ≥2 and B symptom-positive groups compared to their corresponding counterparts in newly diagnosed patients.

Conclusion: Taken together, higher peripheral blood IFN-γ/IL-4 Th2 lymphocytes might be associated with a favorable prognosis like lower rate of relapse in lymphoma patients.
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http://dx.doi.org/10.1080/08820139.2020.1840583DOI Listing
November 2020

The Effects of Low HER2/neu Expression on the Clinicopathological Characteristics of Triple-Negative Breast Cancer Patients.

Asian Pac J Cancer Prev 2020 Oct 1;21(10):3027-3032. Epub 2020 Oct 1.

Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer (BC), and its diagnosis is associated with negative expression of hormone receptors and HER2/neu. It consists of 10-20% of all BCs diagnosed.

Methods And Materials: This study focuses on three groups with different pathology: group one showed complete triple-negative HER2 expression with IHC of BC; groups two and three included patients with ER-, PR-, and HER21+, and ER-, PR-, and HER22+ with a negative FISH test. These three groups were compared from the point of prognosis, which consisted of tumor size, patients' age, lymphatic, vascular and perineural invasion, organ metastasis, number of lymph nodes involvement, and the survival rate.

Results: A total of 459 TNBC patients were enrolled, of which 268 were placed in the HER20 group, 146 in the HER21+ group, and 45 in the HER22+ group. Distant metastasis and recurrence rate were more common in HER20 patients, but bone metastasis was more common in patients with low HER2 expression. All patients with HER20 had a smaller tumor size at the time of BC diagnosis in comparison to patients in the low HER2 expression group. Patients with HER22+ had less lymphatic and vascular invasion as well as axillary lymph nodes involvement, but larger tumor size at presentation, resulting in a lower rate of recurrence and higher overall survival.

Conclusion: The findings revealed that patients with HER22+ had better outcome in comparison to the patients with HER20 and HER21+. Furthermore, the results showed that many patients with HER22+ expression were not basal-like and had good prognosis amongst TNBC patients.
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http://dx.doi.org/10.31557/APJCP.2020.21.10.3027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798168PMC
October 2020

Glucocorticoid induced diabetes and lipid profiles disorders amongst lymphoid malignancy survivors.

Diabetes Metab Syndr 2020 Nov-Dec;14(6):1645-1649. Epub 2020 Aug 26.

Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background And Aims: Hyperglycemia and glucose test abnormalities are problems during the treatment of patients with lymphoid malignancy, caused by corticosteroid therapy. However, its long-term complications or risk of developing diabetes are not available.

Methods: Two hundred patients with lymphoid hematologic malignancy were recruited and followed up for median of 47 months. The underlying hematologic malignancy includes Hodgkin's disease (HD), Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia(CLL), Multiple Myeloma (MM) and Acute Lymphocytic Leukemia (ALL). Fasting blood sugar, glucose tolerance test and lipid profiles were measured before each chemotherapy cycle and every 3 months after. This study was designed to evaluate patients for long-term follow up of glucose tests abnormalities.

Results: The mean age of the non-diabetic patients was significantly lower than that of diabetics and patients with fasting glucose disorder (p < 0.001). The prevalence of diabetes and impaired FBS and GTT was higher in NHL (9%), CLL (6.5%) and MM (1.5%), respectively. For lipid profiles, the highest levels of cholesterol and triglycerides were observed in multiple myeloma and the lowest in Hodgkin's lymphoma (P:0.004).

Conclusions: The most important factor for steroid-induced diabetes is age, which was more prevalent with age increase (P < 0.001). Glucocorticoid-induced diabetes is common in multiple myeloma and then in chronic lymphocytic leukemia and non-Hodgkin's lymphoma in comparison with Hodgkin's lymphoma and acute lymphoblastic leukemia.
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http://dx.doi.org/10.1016/j.dsx.2020.08.027DOI Listing
August 2020

Systematic Evaluation of PKH Labelling on Extracellular Vesicle Size by Nanoparticle Tracking Analysis.

Sci Rep 2020 06 12;10(1):9533. Epub 2020 Jun 12.

Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, United States.

Extracellular vesicles (EVs) are membrane vesicles secreted by cells and can modulate biological activities by transferring their content following uptake into recipient cells. Labelling of EVs is a commonly used technique for understanding their cellular targeting and biodistribution. A reliable fluorescent technique needs to preserve the size of EVs since changes in size may alter their uptake and biodistribution. Lipophilic fluorescent dye molecules such as the PKH family have been widely used for EV labelling. Here, the effect of PKH labelling on the size of EVs was systematically evaluated using nanoparticle tracking analysis (NTA), which is a widely used technique for determining the size and concentration of nanoparticles. NTA analysis showed a size increase in all the PKH labelling conditions tested. As opposed to lipophilic dye molecules, no significant shift in the size of labelled EVs was detected with luminal binding dye molecules such as 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFDA-SE, hereinafter CFSE). This finding suggests that PKH labelling may not be a reliable technique for the tracking of EVs.
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http://dx.doi.org/10.1038/s41598-020-66434-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293335PMC
June 2020

Tangential flow microfluidics for the capture and release of nanoparticles and extracellular vesicles on conventional and ultrathin membranes.

Adv Mater Technol 2019 Nov 20;4(11). Epub 2019 Sep 20.

Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, NY, United States.

Membranes have been used extensively for the purification and separation of biological species. A persistent challenge is the purification of species from concentrated feed solutions such as extracellular vesicles (EVs) from biological fluids. We investigated a new method to isolate micro- and nano-scale species termed tangential flow for analyte capture (TFAC), which is an extension of traditional tangential flow filtration (TFF). Initially, EV purification from plasma on ultrathin nanomembranes was compared between both normal flow filtration (NFF) and TFAC. NFF resulted in rapid formation of a protein cake which completely obscured any captured EVs and also prevented further transport across the membrane. On the other hand, TFAC showed capture of CD63 positive small EVs (sEVs) with minimal contamination. We explored the use of TFAC to capture target species over membrane pores, wash and then release in a physical process that does not rely upon affinity or chemical interactions. This process of TFAC was studied with model particles on both ultrathin nanomembranes and conventional thickness membranes (polycarbonate track-etch). Successful capture and release of model particles was observed using both membranes. Ultrathin nanomembranes showed higher efficiency of capture and release with significantly lower pressures indicating that ultrathin nanomembranes are well-suited for TFAC of delicate nanoscale particles such as EVs.
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http://dx.doi.org/10.1002/admt.201900539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212937PMC
November 2019

Aberrant peripheral blood CD4 CD25 FOXP3 regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma.

Cancer Immunol Immunother 2020 Sep 8;69(9):1917-1928. Epub 2020 May 8.

Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Little is known about the clinical significance of the peripheral blood CD4 CD25 FOXP3 regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both groups. Patients who reached complete remission had elevated frequency of CD4 FOXP3 lymphocytes, Tregs, absolute Treg count, Treg/CD4 and Treg/Th17 ratio in the cHL group and CD4 CD25 cells in DLBCL group. The frequency of Tregs, absolute Treg count and Treg/Th17 ratio in cHL patients and CD4 FOXP3 and CD4 CD25 cells in DLBCL patients positively associated with survival rate. Moreover, the percentage of Tregs and absolute Treg count positively correlated with white blood cell, platelet count and ESR level in cHL patients and with white blood cell count in DLBCL patients. The initial number of Tregs/Th17 cells and also the Treg/Th17 ratio was not associated with changes in disease-free survival (DFS) in both groups. Therefore, higher frequency of peripheral blood Tregs and Treg/Th17 ratio might be associated with a favorable outcome in lymphoma patients, better response to chemotherapy and lower rate of relapse.
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http://dx.doi.org/10.1007/s00262-020-02591-yDOI Listing
September 2020

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc.

Front Bioeng Biotechnol 2020 17;8:311. Epub 2020 Apr 17.

Department of Biomedical Engineering, Rochester Institute of Technology (RIT), Rochester, NY, United States.

Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVD-derived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.
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http://dx.doi.org/10.3389/fbioe.2020.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181459PMC
April 2020

The Effect of ACE Inhibitor on the Quality of Life amongst Patients with Cancer Cachexia.

Asian Pac J Cancer Prev 2020 Feb 1;21(2):325-330. Epub 2020 Feb 1.

Hematology Research Center, Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: ACEI (Angiotensin Converting Enzyme Inhibitors) inhibits tumor growth and development. Different mechanisms have been proposed for this matter, including the inhibition of enzymes that are involved in extracellular matrix degradation, matrix metalloproteinase (MMP) and etc. The present study was designed with the aim to investigate the effects of low dose ACEI on the Quality of Life (QoL) of non-hospitalized gastric cancer patients with cachexia.

Materials And Methods: This study was a single-blinded randomized controlled clinical trial conducted in clinics affiliated with Shiraz University of Medical Sciences (SUMS). All participants were patients with gastric cancer in cancer cachexia step aged 40-80 years old who had referred to our clinics from October 2013 to April 2014. In the intervention group, patients were assigned to receive ACEI (Captopril) and the placebo group served as control and received placebo during the same time course. They were asked questions in order to fill out QLQ-C30 (Persian Version) questionnaire 3 times; baseline, 1 and 2 months after their first visit.

Results: The mean age of patients was 60.55 ± 12.07 (range 31-80) years and the mean BMI of the patients was 17.21 ± 2.31. In the ACEI group, physical functioning and fatigue score changes were significant 1 and 2 months after treatment. The mean of fatigue score decreased significantly in the placebo group. Overall, global health status scores significantly increased in both groups, but other items of QoL did not change significantly.

Conclusion: Overall, our results showed that Captopril does not have a significant positive effect on QoL of patients with cancer cachexia.
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http://dx.doi.org/10.31557/APJCP.2020.21.2.325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332150PMC
February 2020

Validation and Clinical Applications of a Comprehensive Next Generation Sequencing System for Molecular Characterization of Solid Cancer Tissues.

Front Mol Biosci 2019 25;6:82. Epub 2019 Sep 25.

Division of Oncology, Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, United States.

Identification of somatic molecular alterations in primary and metastatic solid tumor specimens can provide critical information regarding tumor biology and its heterogeneity, and enables the detection of molecular markers for clinical personalized treatment assignment. However, the optimal methods and target genes for clinical use are still being in development. Toward this end, we validated a targeted amplification-based NGS panel (Oncomine comprehensive assay v1) on a personal genome machine sequencer for molecular profiling of solid tumors. This panel covers 143 genes, and requires low amounts of DNA (20 ng) and RNA (10 ng). We used 27 FFPE tissue specimens, 10 cell lines, and 24 commercial reference materials to evaluate the performance characteristics of this assay. We also evaluated the performance of the assay on 26 OCT-embedded fresh frozen specimens (OEFF). The assay was found to be highly specific (>99%) and sensitive (>99%), with low false-positive and false-negative rates for single-nucleotide variants, indels, copy number alterations, and gene fusions. Our results indicate that this is a reliable method to determine molecular alterations in both fixed and fresh frozen solid tumor samples, including core needle biopsies.
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http://dx.doi.org/10.3389/fmolb.2019.00082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798036PMC
September 2019

Optimization of CuInGaS Nanoparticles and Their Application in the Hole-Transporting Layer of Highly Efficient and Stable Mixed-Halide Perovskite Solar Cells.

ACS Appl Mater Interfaces 2019 Aug 13;11(34):30838-30845. Epub 2019 Aug 13.

Research Department of Nano-Technology and Advanced Materials , Materials and Energy Research Center , Karaj 31787-316 , Iran.

Inorganic hole-transport materials (HTMs) have been frequently applied in perovskite solar cells (PSCs) and are a promising solution to improve the poor stability of PSCs. In this study, we investigate solution-processed copper indium gallium disulfide (CIGS) nanocrystals (NCs) as a dopant-free inorganic HTM in n-i-p type PSCs. Moreover, Cs(MA-FA)Pb(IBr) mixed-halide perovskite with proper crystalline quality and long-time stability was utilized as the light-absorbing layer under ambient conditions. To optimize the cell performance and better charge extraction from the perovskite layer, the Ga concentration in the Cu(InGa)S composition was changed, and the value was altered between 0.0 and 0.75. It was shown that the CIGS band gap enhances with increasing Ga content; thus, with tunable band gaps and engineering of the energy level alignment, a better collection of photogenerated holes and a reduced electron-hole recombination rate could be achieved. The maximum power conversion efficiency of 15.6% was obtained for the PSC with Cu(InGa)S hole-transport layer composition, which is the highest efficiency reported so far for CIGS-based dopant-free PSCs. This value is very close to the efficiency of devices fabricated with doped spiro-OMeTAD as an organic HTM. Additionally, the stability of nonencapsulated PSCs was studied, and CIGS-based devices demonstrated 70% retention after 90 days of aging in the dark and in 50% relative humidity conditions. This result is quite better than the similar measurements for the doped spiro-OMeTAD-based devices.
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http://dx.doi.org/10.1021/acsami.9b08714DOI Listing
August 2019

Sensitization and Geographical Distribution of Main Aeroallergens in Iran.

Iran J Allergy Asthma Immunol 2018 Oct 7;17(5):497-501. Epub 2018 Oct 7.

Department of Immunology, Microbiology and Parasitology, Faculty of Pharmacy and Laboratory of Parasitology and Allergy, Lascaray Research Centre, University of the Basque Country, Vitoria, Spain.

N0 Abstract.
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October 2018

An Unusual Case Report: Occurrence of Renal Cell Carcinoma, Basal Cell Carcinoma and Chronic Lymphocytic Leukemia in a Case of Papillary Thyroid Carcinoma Treated with Radioactive Iodine.

Iran J Med Sci 2018 Nov;43(6):659-663

Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran.

The standard therapy for thyroid cancer is total or near total thyroidectomy, followed by the administration of radioactive iodine for remnant ablation or residual disease. Patients with radioiodine therapy are predisposed to second malignant neoplasms in organs such as central nervous system (CNS), breast, prostate, kidney, bone marrow, salivary gland, and digestive tract. Exposure to carcinogen including occupational and therapy related hazard, aging and genetic susceptibility are other causes of second primary cancers. The second primary malignancies are not uncommon and, nowadays, the prevalence of it is mildly increasing due to the increasing survival of cancer patients and advances in early diagnosis and therapeutic modalities. Here, we present a fifty-one-year-old man with papillary thyroid carcinoma (PTC), who developed chronic lymphocytic leukemia (CLL), renal cell carcinoma (RCC), and basal cell carcinoma (BCC) in 15-20 years after radioactive iodine therapy. Second primary tumors are increasing and environmental, genetic susceptibility and increase in survival of cancer patients are the major risk factors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230934PMC
November 2018

Association of single nucleotide autophagy-related protein 5 gene polymorphism rs2245214 with susceptibility to non-small cell lung cancer.

J Cell Biochem 2018 Sep 22. Epub 2018 Sep 22.

Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

Introduction: Autophagy is a mechanism that is involved in the regulation of cellular life, apoptosis, and stemness while its intervening genes play important functions in various cancers including lung cancer. ATG5 is one of the key genes for the regulation of the autophagy pathway. In this study, our team has investigated the potential relationship between ATG5 gene polymorphism rs2245214 with non-small cell lung cancer (NSCLC) in a subpopulation of patients from southern Iran. In this study, 34 patients with NSCLC (20 males and 14 females [mean age: 12.86 ± 60.47 years]) and 50 healthy subjects (30 males and 20 females [mean age: 13.09 ± 56.62 years]) were studied in terms of the genotype of the ATG5 gene. We used restriction fragment length polymorphism and analyzed the results using SPSS software (v.23). The results revealed that subjects harboring the guanine/cytosine (GC) genotype of the rs2245214 ATG5 gene polymorphism had suffered less from NSCLC, whereas the prevalence of the C-allele of this polymorphism was significantly higher in patients with NSCLC ( P < 0.05). On the basis of the results of logistic regression, the presence of this C-allele may predict the risk of lung cancer ( P value = 0.011; OR, 3.52; 95% CI, 1.33-9.26). This study concludes that the C-allele of the rs2245214 ATG5 gene polymorphism is associated with increased susceptibility to NSCLC, whereas the GC genotype of this polymorphism is associated with decreased risk and might therefore have a protective role in the development of NSCLC.
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http://dx.doi.org/10.1002/jcb.27467DOI Listing
September 2018

A comparative study on the effects of acute and chronic downhill running vs uphill running exercise on the RNA levels of the skeletal muscles PGC1-α, FNDC5 and the adipose UCP1 in BALB/c mice.

Gene 2018 Dec 13;679:369-376. Epub 2018 Sep 13.

Division of Cellular and Molecular Biology, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran; Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Electronic address:

The purpose of this study was to investigate the effect of a single bout and 8 weeks of downhill running versus uphill running exercise on expression of PGC1-α, FNDC5 and UCP1 in mice. Forty-eight BALB/c male mice weighing 25-30 g were randomly assigned into 8 groups: 1) acute downhill running (ADR) on a -15° slope; 2) acute uphill running (AUR) on a +15° slope; 3) acute running without inclination (AWI), 4) acute without exercise as control (ACtrl), 5) chronic downhill running (CDR) on a -15° slope; 6) chronic uphill running (CUR) on a +15°slope; 7) chronic running without inclination (CWI), 8) chronic without exercise as control (CCtrl). Twenty four hours after the last training session, the mice were sacrificed and Calf muscles (including soleus and gastrocnemius) and quadriceps muscles (including Rectus femoris and vastus intermedius) were obtained and expression levels of PGC1-α and FNDC5 in crus and quadriceps muscles and UCP1 in visceral and subcutaneous adipose tissues were measured and compared between the groups. PGC-1α and FNDC5 mRNA levels increased after treadmill exercise training in all acute and chronic exercise groups in both skeletal muscle groups. Furthermore mRNA level of UCP1 in subcutaneous adipose tissue but not in visceral adipose tissue increased both after acute and chronic exercise. Collectively, data showed that downhill running exercise to be more effective than other exercises, as downhill running has led to a greater improvement in metabolism may be considered more effective for browning of fat tissue.
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http://dx.doi.org/10.1016/j.gene.2018.09.024DOI Listing
December 2018

Klotho inhibits EGF-induced cell migration in Caki-1 cells through inactivation of EGFR and p38 MAPK signaling pathways.

Oncotarget 2018 Jun 1;9(42):26737-26750. Epub 2018 Jun 1.

Division of Oncology, Department of Internal Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas 77030, United States of America.

Klotho is a single-pass transmembrane protein with documented anti-cancer properties. Recent reports have implicated Klotho as an inhibitor of transforming growth factor β1 induced cell migration in renal fibrosis. Overexpression of epidermal growth factor receptor (EGFR) is known to promote tumor initiation and progression in clear-cell renal cell carcinoma (cRCC). We tested our hypothesis that Klotho inhibits EGF-mediated cell migration in cRCC by interfering with the EGFR signaling complex and mitogen-activated protein kinase (MAPK) pathways. We performed cell adhesion, migration, and biochemical studies using Caki-1 cell line. In addition, we validated the cell culture studies with expression analysis of six de-identified FFPE tissues from primary and metastatic cRCC patients. Our studies show that Klotho inhibited EGF-induced Caki-1 de-adhesion and decreased spreading on collagen type 1. Klotho also inhibited EGF-induced α2β1 integrin-dependent cell migration on collagen type 1. To test the involvement of MAPK pathways in EGF-induced Caki-1 cell motility, the cells were pretreated with either SB203580, a specific p38 MAPK inhibitor, or Klotho. SB203580 blocked the EGF-induced Caki-1 cell migration. Klotho had a comparable inhibitory effect. Our FFPE clinical specimens revealed decreased Klotho mRNA expression compared to a control, non-cancer kidney tissue. The decrease in Klotho mRNA levels correlated with increased c-Src expression, while E-Cadherin was relatively reduced in metastatic FFPE specimens where Klotho was least expressed. Taken together, these results suggest that secreted Klotho inhibits EGF-induced pro-migratory cell morphological changes and migration in Caki-1 cells. Our data additionally suggest that decreased Klotho expression may be involved in cRCC metastasis.
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http://dx.doi.org/10.18632/oncotarget.25481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003560PMC
June 2018

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer.

Int J Genomics 2018 22;2018:4863757. Epub 2018 Mar 22.

Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

Background And Purpose: The mevalonate pathway is one of the major metabolic pathways that use acetyl-CoA to produce sterols and isoprenoids. These compounds can be effective in the growth and development of tumors. One of the enzymes involved in the mevalonate pathway is FDFT1. Different variants of this gene are involved in the risk of suffering various diseases. The present study examined the relationship between FDFT1 rs2645429 polymorphism and the risk of nonsmall cell lung cancer (NSCLC) in a population from southern Iran.

Method: The genotypes of rs2645429 polymorphism of FDFT1 gene were examined in 95 samples: 34 patients with NSCLC and 61 healthy individuals by RFLP method.

Results: The results of this study indicated that C allele of this polymorphism was effectively associated with the risk of NSCLC in the Iranian population ( value = 0.023; OR = 2.71; 95% CI = 1.12-6.59) and CC genotype has significant relation with susceptibility to NSCLC ( value = 0.029; OR = 3.02; 95% CI = 1.09-8.39). This polymorphism is located in the promoter region FDFT1 gene, and CC genotype may increase the activity of this promoter. This study also found a significant relationship between C allele and metastatic status. C allele was more common in NSCLC patients. ( = 0.04).

Conclusion: C allele of FDFT1 rs2645429 polymorphism gene can be a risk factor for NSCLC, whereas T allele probably has a low protective role.
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http://dx.doi.org/10.1155/2018/4863757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885393PMC
March 2018

Glomus tumor as a cause of oncogenic osteomalacia.

Clin Cases Miner Bone Metab 2017 Sep-Dec;14(3):359-362. Epub 2017 Dec 27.

Medical Imaging Research Center, Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Many tumors that occasionally are benign in origin causes hypophosphatemic osteomalacia. Here we present a case of glomus tumor in a 59-year-old man with oncogenic osteomalacia. Diagnosis was made after observation of abnormal increase activity in octreotide scan. The magnetic resonance imaging showed a round lesion in left ankle joint. Surgical excision of tumor was curative and all symptoms and intractable hypophosphatemia improved after few weeks.
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http://dx.doi.org/10.11138/ccmbm/2017.14.3.359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762230PMC
December 2017

Grafting with Cryopreserved Amniotic Membrane versus Conservative Wound Care in Treatment of Pressure Ulcers: A Randomized Clinical Trial.

Bull Emerg Trauma 2017 Oct;5(4):249-258

Transplant Research Center, Shiraz Institute for Stem Cell and Regenerative Medicine, Shiraz University of Medical Science, Shiraz, Iran.

Objective: To compare the healing process of pressure ulcers treated with cryopreserved human amniotic membrane allograft and routine pressure ulcer care in our hospital.

Methods: From January 2012 to December 2013, in a prospective randomized clinical trial (IRCT201612041335N2), 24 patients with second and third stage of pressure ulcers were enrolled in this study. All patients needed split-thickness skin grafts for pressure ulcer-wound coverage. Selected patients had symmetric ulcers on both upper and lower extremities. The patients were randomly divided into two groups: amnion and control. In the amnion group, the ulcer was covered with cryopreserved amniotic membrane and in the control group it was treated with local Dilantin powder application. The duration and success rate of complete healing was compared between the two groups.

Results: The study group was composed of 24 pressure ulcers in 24 patients (19 males and 5 females) with a mean age of 44±12.70 years. The demographic characteristics, ulcer area, and underlying diseases were similar in both groups. The early sign of response, such as decrease in wound discharge, was detected 12-14 days after biological dressing. Complete pressure ulcer healing occurred only in the amnion group (< 0.001). Partial healing was significantly higher in the amnion group (< 0.03). Healing time in this group was faster than that the control group (20 days versus 54 days). No major complication was recorded with amniotic membrane dressing.

Conclusion: Cryopreserved amniotic membrane is an effective biologic dressing that promotes re-epithelialization in pressure ulcers.
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http://dx.doi.org/10.18869/acadpub.beat.5.4.452.DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694597PMC
October 2017

Pegfilgrastim Versus Filgrastim for Primary Prophylaxis of Febrile Neutropenia in Patients with non-Hodgkin’s Lymphoma: A Cost-Effectiveness Study

Asian Pac J Cancer Prev 2017 10 26;18(10):2703-2707. Epub 2017 Oct 26.

Department of Health Services Management, School of Management and Medical Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Aim: One method to deal with febrile neutropenia is the use of granulocyte colony stimulating factors (G-CSFs). Pegfilgrastim or Filgrastim injection can lead to a reduction in febrile neutropenia and severe neutropenia in patients receiving chemotherapy. This study aimed to compare the cost-effectiveness of using Pegfilgrastim, 3-day Filgrastim and 1-day Filgrastim medication strategies for the primary prophylaxis of febrile neutropenia in patients with relapsed non-Hodgkin’s lymphoma after salvage chemotherapy who referred to two referral centers affiliated to Iran, Shiraz University of Medical Sciences in 2014. Method: This cost-effectiveness study was conducted on 131 patients with non-Hodgkin’s lymphoma. The outcome of the study was the prevention of febrile neutropenia. The cost data were collected from the health payer’s perspective for each medication strategy by reviewing the patients’ medical records and using expert opinion. The results were presented in terms of the incremental cost-effectiveness ratio (ICER) and the sensitivity analysis was used to assess the robustness of results. In this study, the collected data were analyzed using Excel 2007 and Tree-age 2011. Results: The results showed that the degrees of febrile neutropenia prevented by Pegfilgrastim, 3-day Filgrastim and 1-day Filgrastim strategies were 0.97, 0.95 and 0.83, respectively, and the average annual costs of hospitalization per patient were, 5299, 4959 and 5808 PPP$. Conclusion: The results showed that while 1-day Filgrastim was absolutely predominant, using the 3-day Filgrastim and Pegfilgrastim strategies were more cost-effective. Therefore, they can be recommended respectively as the first and second treatment priorities in patients with non-Hodgkin’s lymphoma after salvage chemotherapy.
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http://dx.doi.org/10.22034/APJCP.2017.18.10.2703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747393PMC
October 2017

Spontaneous rupture of continent cutaneous urinary diversion after 25 years.

J Renal Inj Prev 2017 19;6(2):80-82. Epub 2016 Nov 19.

Department of Epidemiology, Zabol University of Medical Science, Zabol, Iran.

Spontaneous rupture of a continent cutaneous urinary diversion is uncommon and diagnosis of this situation requires a high degree of suspicion. In this paper we present a 66-year-old man with continent cutaneous pouch after radical cystoprostatectomy that presented with spontaneous perforation 25 years after surgery. Spontaneous pouch perforation in our case after 25 years emphasizes the need for long follow-up in patients with continent diversion.
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http://dx.doi.org/10.15171/jrip.2017.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423288PMC
November 2016

Comparison of Ifosfamide, Carboplatin and Etoposide versus Etoposide, Steroid, and Cytarabine Cisplatin as Salvage Chemotherapy in Patients with Refractory or Relapsed Hodgkin's lymphoma.

Adv Biomed Res 2017 7;6:30. Epub 2017 Mar 7.

Medical School, Research Deputy of Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Refractory or relapsed Hodgkin's disease (HD) occurs in 10-50% of patients. The treatment of choice for these patients is high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Response to salvage chemotherapy (SCT) partial remission (PR) is necessary before HDCT with ASCT. However, its applicability is restricted mostly to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy profiles of ifosfamide, carboplatin, and etoposide (ICE) and etoposide-steroid-cytarabine-cisplatin (ESHAP) (cytosine arabinoside, cisplatin, and dexamethasone) regimens in the salvage treatment of relapsed or refractory HD.

Materials And Methods: In this retrospective analysis, 114 patients with primary refractory or relapsed HD who received ICE or ESHAP salvage regimen were included.

Results: Of 114 patients, 47 (41.2%) were females and the median age was 31.5 years. Response could be evaluated in 114 patients. Of 114 patients, 38 (33%) achieved complete remission (CR) and 21 (18.4%) achieved PR, leading to an overall response rate (ORR: CR + PR) of 51.4%. In the evaluable ICE group ( = 41), rates of CR, PR, and ORR were 21.9%, 17.1%, and 39% and in the ESHAP group ( = 73), rates of CR, PR, and ORR were 39.7%, 19.2%, and 58.9% (for ORR, = 0.04), respectively.

Conclusion: In patients with relapsed or refractory HD, treatment with ESHAP seems to have higher rates of response than ICE regimen does.
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http://dx.doi.org/10.4103/2277-9175.201687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360016PMC
March 2017

Economic Burden of Avoidable Hospitalizations among Patients with Cancer at Namazi Hospital in Shiraz, 2013

Asian Pac J Cancer Prev 2017 01 1;18(1):177-182. Epub 2017 Jan 1.

Department of Health Service Administration, School of Management and Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Email:

Introduction: Hospitalization of patients with cancer has a significant economic impact and avoidance where unnecessary has great potential for significant cost savings for patients, individual hospitals and the health system in general. Methods: Demographic, clinical and economical data were collected from medical records in our hospital retrospectively. Oncology clinicians reviewed medical records to categorize each hospitalization as “potentially avoidable” or “not avoidable.” Patient demographic and clinical data were abstracted and quantitative and qualitative analyses were performed to identify patient characteristics and outcomes associated with potentially avoidable hospitalizations. Finally data on the cost of the latter were estimated. Results: Of 451 hospitalizations, medical oncologists identified 55 (12.2%) as potentially avoidable. Avoiding these and caring for the patients in alternative locations would save some $ US 641,240 yearly. Among patients with avoidable hospitalization, 70.9% were males and the median age and median length of stay was 55 years and 4.7 days. Most of them had general signs (83.6%) and a fever body temperature lower than 38.5’C (96.4%). Lung, kidney and urinary tract cancers were the most common diagnoses (10.9%). The majority of avoidable hospitalized patients had local cancer (85.5%) and poor performance status (43.6%). The most prevalent procedure for patients with avoidable hospitalization was sonography and the least frequent were laboratory tests and MRI. Most cases received no treatment. Conclusion: Avoidable hospitalizations are common in patients with cancer. Age, final results of hospitalization and length of stay were established as significant variables for patients with avoidable hospitalization.
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http://dx.doi.org/10.22034/APJCP.2017.18.1.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563097PMC
January 2017

Correction: GDP versus ESHAP Regimen in Relapsed and/or Refractory Hodgkin lymphoma: A Comparison Study.

Int J Hematol Oncol Stem Cell Res 2015 Oct;9(4):218

Department of Medical Oncology and Hematology and Bone Marrow Transplantation, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748694PMC
October 2015