Publications by authors named "Bahram Memar"

69 Publications

Elucidated tumorigenic role of MAML1 and TWIST1 in gastric cancer is associated with Helicobacter pylori infection.

Microb Pathog 2021 Nov 21:105304. Epub 2021 Nov 21.

Medical Genetics Research Center, Faculty of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Epithelial-mesenchymal transition (EMT) has a fundamental role in tumor initiation, progression, and metastasis. Helicobacter pylori (HP) induces EMT and thus causes gastric cancer (GC) by deregulating multiple signaling pathways involved in EMT. TWIST1 and MAML1 have been confirmed to be critical inducers of EMT via diverse signaling pathways such as Notch signaling. This study aimed to investigate for the first time possible associations between TWIST1/MAML1 mRNA expression levels, HP infection, and clinicopathological characteristics in GC patients.

Method: TWIST1 and MAML1 mRNA expression levels were evaluated in tumoral and adjacent normal tissues in 73 GC patients using the quantitative reverse transcription PCR (RT-qPCR) method. PCR technique was also applied to examine the infection with HP in GC samples.

Results: Upregulation of TWIST1 and MAML1 expression was observed in 35 (48%) and 34 (46.6%) of 73 tumor samples, respectively. Co-overexpression of these genes was found in 26 of 73 (35.6%) tumor samples; meanwhile, there was a significant positive correlation between MAML1 and TWIST1 mRNA expression levels (P < 0.001). MAML1 overexpression exhibited meaningful associations with advanced tumor stages (P = 0.006) and nodal metastases (P ˂ 0.001). 34 of 73 (46.6%) tumors tested positive for HP, and meanwhile, MAML1 expression was positively related with T (P = 0.05) and grade (P = 0.0001) in these HP-positive samples. Increased TWIST1 expression was correlated with patient sex (P = 0.035) and advanced tumor grade (P = 0.017) in HP-infected tumors. Furthermore, TWIST1 and MAML1 expression levels were inversely linked with histologic grade in HP-negative tumor samples (P = 0.021 and P = 0.048, respectively).

Conclusion: We propose TWIST1 and MAML1 as potential biomarkers of advanced-stage GC that determine the characteristics and aggressiveness of the disease. Based on accumulating evidence and our findings, they can be introduced as promising therapeutic targets to modify functional abnormalities in cells that promote GC progression. Moreover, HP may enhance GC growth and metastasis by disrupting TWIS1/MAML1 expression patterns and related pathways.
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http://dx.doi.org/10.1016/j.micpath.2021.105304DOI Listing
November 2021

Effects of Sertraline on Spermatogenesis of Male Rats and its Reversibility after Terminating the Drug.

Urol J 2021 Apr 4;18(4):434-438. Epub 2021 Apr 4.

Resident, Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Purpose: The purpose of this research was to studding the effects of Sertraline on spermatogenesis of male rats and whether these probable effects are constant or provisional after terminating the drug.

Materials And Methods: In this study, 32  two-month old male Wistar albino rats were equally divided into the Sertraline-treated and the control groups. The drug group was gavaged with Sertraline daily while the control group was gavaged with water at the same volume. After 80 days, half of the rats in each group were selected randomly for hormonal evaluations and bilateral orchiectomy. Histological and hormonal evaluations were performed. The remaining half of rats were kept alive for 90 more days without intervention and then underwent hormonal evaluation and bilateral orchiectomy in a similar fashion.

Results: There was no difference between the testes histology and pathology of the sertraline-treated and the control groups.  There was a significant decrease in serum FSH in the Sertraline-treated group compared to the control group (P <0.05). However, this decline appeared to be reversible following termination of exposure to Sertraline. FSH returned to pretreatment levels in the remaining treated rats following 90 days of treatment cessation.  Conclusion: Within the time-frame studied, Sertraline can induce transitory changes in serum FSH of male rats without concomitant spermatogenic changes within the testes.  This hormonal change appears to be reversible following withholding of Sertraline. The long-term effect of Sertraline usage on hormonal status and spermatogenesis in rats needs further investigation.
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http://dx.doi.org/10.22037/uj.v18i.6458DOI Listing
April 2021

The accuracy of sentinel node biopsy by Tc-sodium phytate in patients with pancreatic cancer.

Ann Hepatobiliary Pancreat Surg 2020 Aug;24(3):277-282

Nuclear Medicine Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

Backgrounds/aims: Pancreaticoduodenectomy is the only potentially curative treatment for pancreatic cancer. The identification of the first nodal drainage site (sentinel node) may improve the detection of metastatic nodes and can contribute to a less invasive surgery. We aimed to determine the accuracy of sentinel node mapping in patients with pancreatic cancer using intraoperative radiotracer injection technique.

Methods: At surgical exposure, peritumoral injection of 0.4-0.5 mci/0.5 ml of 99mTc- sodium phytate was performed. After tumor resection, sentinel nodes were investigated in the most common areas using a hand-held gamma probe. Any lymph node with in vivo count twice the background was considered as sentinel node, thus, it was removed and sent for pathological assessment. Then a standard lymph node dissection was performed for all patients.

Results: Fourteen patients with cancer in the head of the pancreas were included in this study. Overall, 180 lymph nodes were harvested with a mean of 11.6±4.7 lymph nodes per patient. In eight patients, at least one sentinel node could be identified (detection rate about 64%). False negative rate of the study was 3/5 (60%).

Conclusions: Our study revealed insufficient diagnostic accuracy and high false negative rate for sentinel lymph node mapping with 99mTc- sodium phytate in pancreatic cancer.
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http://dx.doi.org/10.14701/ahbps.2020.24.3.277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452803PMC
August 2020

GSTs polymorphisms are associated with epigenetic silencing of CDKN2A gene in esophageal squamous cell carcinoma.

Environ Sci Pollut Res Int 2020 Sep 1;27(25):31269-31277. Epub 2020 Jun 1.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Esophageal cancer is the eighth most common cancer and the sixth most frequent cause of cancer mortality worldwide. Exposure to polycyclic aromatic hydrocarbons formed by incomplete combustion of organic matter is an important risk factor. Genetic polymorphisms in genes encoding PAH-metabolizing enzymes like glutathione S-transferases (GSTM1, GSTP1, GSTT1) which conjugate glutathione to PAHs for reduction of oxidative stress may affect an individual's response to PAH exposure. Genomic DNA from 50 esophageal squamous cell carcinoma patients extracted from peripheral blood. PCR-RFLP technique was employed to determine GSTM1, GSTT1, and GSTP1 polymorphisms. Aberrant promoter methylation of CDKN2A was applied by methylation-specific PCR technique. Concentration of urinary 1-hydroxypyrene was determined using a HPLC system. About 38.7% showed the null GSTM1 genotype (54% cases and 13% controls), 23.7% showed GSTT1 null genotype (30% cases and 13% controls), and 62.5% were GSTP1 A/A genotype (66% cases and 56% controls). Polymorphic variants of GSTM1 and GSTT1 were significantly associated with aberrant methylation of CDKN2A gene. The null state of GSTT1 was significantly associated with high concentrations of 1-OHP in urea (p < 0.01). There was significant association between methylated states of CDKN2A and high concentrations of 1-OHP in urine (p < 0.01). We identified significant association between polymorphism of GSTs genes and epigenetic silencing of tumor suppressor gene CDKN2A in esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1007/s11356-020-09408-6DOI Listing
September 2020

Role of MAML1 in targeted therapy against the esophageal cancer stem cells.

J Transl Med 2019 04 16;17(1):126. Epub 2019 Apr 16.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Esophageal cancer is the sixth-leading cause of cancer-related deaths worldwide. Cancer stem cells (CSCs) are the main reason for tumor relapse in esophageal squamous cell carcinoma (ESCC). The NOTCH pathway is important in preservation of CSCs, therefore it is possible to target such cells by targeting MAML1 as the main component of the NOTCH transcription machinery.

Methods: In present study we isolated the CD44+ ESCC CSCs and designed a MAML1-targeted therapy to inhibit the NOTCH signaling pathway. CSCs were isolated using magnetic cell sorting utilizing the CD44 cell surface marker. Several stem cell markers were analyzed in the levels of protein and mRNA expression. The isolated CSCs were characterized in vivo in NUDE mice. Biological role of MAML1 was assessed in isolated CD44+ CSCs. A drug resistance assay was also performed to assess the role of MAML1 in CD44+ CSCs with 5FU resistance.

Results: The CD44+ CSCs had ability to form tumors in NUDE mice. MAML1 silencing caused a significant decrease (p = 0.019) and ectopic expression caused a significant increase in migration of CD44+ CSCs (p = 0.012). Moreover, MAML1 silencing and ectopic expression significantly increased and decreased 5FU resistance, respectively (p < 0.05). MAML1 silencing significantly increased the number of cells in G1 phase (p = 0.008), and its ectopic expression significantly increased the number of CD44+ CSCS in S phase (p = 0.037).

Conclusions: MAML1 may be utilized for targeted therapy with a low side effect to eliminate the CD44+ CSCs through inhibition of canonical NOTCH pathway in ESCC patients.
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http://dx.doi.org/10.1186/s12967-019-1876-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469193PMC
April 2019

Induction of T cell-mediated immune response by dendritic cells pulsed with mRNA of sphere-forming cells isolated from patients with gastric cancer.

Life Sci 2019 Feb 12;219:136-143. Epub 2019 Jan 12.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-γ) gene expression and specific cytotoxicity. Spheroid colonies were formed in serum-free media. Sphere-forming cells dissociated from tumorspheres heterogeneously expressed CD44, CD54, and epithelial cell adhesion molecule (EpCAM) markers and generated one tumor in nude mice. These results demonstrated that gastric CSCs were enriched in tumorspheres. Cytokine-matured DCs loaded with mRNA of sphere-forming cells were able to induce IFN-γ gene expression in T-lymphocytes after a 12-day co-culture. mRNA level of IFN-γ gene in these lymphocytes was more highly expressed compared to stimulated T-lymphocytes by DCs transfected with normal tissue (6.4-9.39 folds). Cytotoxic activity of primed T-lymphocytes with antigens of sphere-forming cells was significantly higher than normal tissue antigens and mock DCs (P ≤ 0.0001). Taken together, DCs loaded with mRNA of sphere-forming cells that elicit effectively specific T cell-mediated immune responses in vitro, may be considered as a promising therapeutic vaccination in GC patients in future.
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http://dx.doi.org/10.1016/j.lfs.2019.01.016DOI Listing
February 2019

ErbB1 and ErbB3 co-over expression as a prognostic factor in gastric cancer.

Biol Res 2019 Jan 8;52(1). Epub 2019 Jan 8.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Epidermal growth factor receptor family members such as ErbB1 and ErbB3 are involved in tumor progression and metastasis. Although, there are various reports about the prognostic value of EGFR members separately in gastric cancer, there is not any report about the probable correlation between ErbB1 and ErbB3 co-expression and gastric cancer prognosis. In present study, we assessed the correlation between ErbB1 and ErbB3 co-overexpression (in the level of mRNA and protein expression) and gastric cancer prognosis for the first time.

Methods: ErbB1 and ErbB3 expressions were analyzed by immunohistochemistry and real-time PCR in 50 patients with gastric cancer. Parametric correlations were done between the ErbB1 and ErbB3 expression and clinicopathological features. Multivariate and logistic regression analyses were also done to assess the roles of ErbB1 and ErbB3 in tumor prognosis and survival.

Results: There were significant correlations between ErbB1/ErbB3 co-overexpression and tumor size (p = 0.026), macroscopic features (p < 0.05), tumor differentiation (p < 0.05), stage of tumor (p < 0.05), and recurrence (p < 0.05). Moreover, ErbB1/ErbB3 co-overexpression may predict the survival status of patients (p < 0.05).

Conclusion: ErbB1 and ErbB3 co-overexpression is accompanied with the poor prognosis and can be used efficiently in targeted therapy of gastric cancer patients.
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http://dx.doi.org/10.1186/s40659-018-0208-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323733PMC
January 2019

A STROBE compliant observational study on trace elements in patients with ulcerative colitis and their relationship with disease activity.

Medicine (Baltimore) 2018 Dec;97(52):e13523

Pathology ward, Razavi Hospital, Mashhad, Iran.

Nutritional deficiencies and malnutrition are considered to be related to ulcerative colitis (UC); however, the association between serum levels of micronutrients and UC is not well known. This study aimed to evaluate the serum levels of micronutrients in UC patients and investigate their association with disease activity.This cross-sectional study was conducted on UC patients visiting the Department of Gastroenterology at 3 different teaching hospitals between January 2016 and January 2017. UC activity was measured based on Truelove and Witts' severity index and guidelines for colonoscopy. A healthy gender- and age-matched group was also selected. Serum levels of zinc, copper, selenium, ceruloplasmin, albumin, and total protein were compared between the 2 groups of UC patients and healthy subjects using independent-samples t test. Also, the association between serum levels of micronutrients and UC activity was assessed by using Pearson and Spearman correlation coefficient tests. The data were analyzed by SPSS version 21, considering P ≤.05 as the statistical significance level.Overall, 112 (54 male and 58 female) individuals with the mean age of 34.6 years were studied in the 2 groups of UC patients (n = 56) and healthy subjects (n = 56). The 2 groups were homogeneous in terms of age, gender, marital status, place of residence, and educational level (P >.05). The serum levels of total protein (6.41 ± 1.1 vs 7.41 ± 0.4 g/dL; P = .0001), albumin (4.72 ± 1.1 vs 5.19 ± 0.28 g/dL; P = .0001), zinc (679 ± 62 vs 1055 ± 156 μg/L; P = .0001), and selenium (81.85 ± 6.4 vs 108.4 ± 12.98 micg/L; P = .0001) were significantly lower in the UC patients. The serum level of copper did not differ significantly between the 2 groups (P = .1).Considering the simultaneous reduction in nutritional criteria in the UC patient group, malnutrition appears to be a factor affecting micronutrient deficiency in patients with UC.
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http://dx.doi.org/10.1097/MD.0000000000013523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314770PMC
December 2018

Immunomodulatory effects of silymarin after subacute exposure to mice: A tiered approach immunotoxicity screening.

J Pharmacopuncture 2018 Jun 30;21(2):90-97. Epub 2018 Jun 30.

Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis.
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http://dx.doi.org/10.3831/KPI.2018.21.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054091PMC
June 2018

Effect of L. stigma (saffron) against subacute effect of diazinon: histopathological, hematological, biochemical and genotoxicity evaluations in rats.

J Pharmacopuncture 2018 Jun 30;21(2):61-69. Epub 2018 Jun 30.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Objective: In this study, the effects of saffron stigma against subacute diazinon (DZN) toxicity on enzymes levels, biochemical, hematological, histopathological and genotoxicity indices were studied in rats.

Methods: Vitamin E (200 IU/kg) and the aqueous extract of saffron (50, 100 and 200 mg/kg) were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The hematological and biochemical parameters were evaluated at the end of 4 weeks.

Results: Reticulocytes counts, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase, CPK-MB, gama glutamyl transferase (GGT), uric acid and micronucleus indices were increased significantly but total protein and RBC cholinesterase activity were decreased in the DZN-treated group. Saffron prevented the effect of DZN on GGT (50 mg/kg), LDH, CPK and CPK-MB (100 and 200 mg/kg) levels. An increased uric acid and reduced protein levels by DZN were prevented by vitamin E and some doses of saffron. A significant reduction was observed in platelets, RBC, hemoglobin and hematocrit indices in the DZN group. Saffron and vitamin E prevented this reduction. Vitamin E and saffron did not reduce the effect of DZN on RBC cholinesterase activity. The extract and vitamin E could not prevent DZN genotoxicity in the micronucleus assay. Other biochemical parameters and pathological evaluation did not show any abnormality in tissues of all groups.

Conclusion: This study shows that vitamin E and saffron reduce DZN induced hematological and biochemical toxicity. However, they do not prevent the genotoxicity induced by DZN.
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http://dx.doi.org/10.3831/KPI.2018.21.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054089PMC
June 2018

Evaluating the expression of cyclooxygenase-2 enzyme by immunohistochemistry in normal and tumoral tissue before and after neoadjuvant chemoradiotherapy in patients with esophageal cancer in Khorasan Province.

J Cancer Res Ther 2018 Apr-Jun;14(3):509-515

Department of Internal Medicine, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Esophageal cancer is the third most common cancer in Iran. Neoadjuvant chemoradiotherapy (NCRT) is the appropriate treatment for esophageal cancer.

Aim: This study investigated the expression of cyclooxygenase (COX)-2 enzyme in normal and tumoral tissues before any treatment in patients with esophageal cancer, this study also assessed the effect of NCRT on the expression of COX-2 enzyme in normal and tumoral tissue in samples derived by surgery furthermore, and this study investigated the relationship between expression of COX-2 enzyme and the pathologic tumor regression grade (PTRG) patients.

Materials And Methods: In this study, a total of 120 patients admitted to Omid Hospital, Imam Reza Hospitals, and Reza-Mashhad Medical Center, who were treated with NCRT, were recruited and the expression of the COX-2 enzyme in normal and tumoral tissues was assessed by immunohistochemistry before and after treatment by an expert pathologist between zero and 300. PTRG was determined by a pathologist after treatment.

Results: The mean levels of COX-2 expression, obtained from tumoral and normal tissue baseline biopsy in patients, were 177.69 and 64.29, respectively, while in surgical specimen were 177.25 and 49.84, respectively. A significant association was found between PTRG of surgical specimen and COX-2 expression in normal tissue (baseline biopsy) at diagnosis (P = 0.034).

Conclusions: The results indicated that expression of COX-2 in tumoral tissues exceeds the expression of COX-2 in normal tissue of the baseline biopsy. Patients with a high expression of COX-2 in baseline tumor biopsies had less response to treatment of pathology compared to patients with lower expression of COX-2 in baseline tumor biopsies.
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http://dx.doi.org/10.4103/0973-1482.199428DOI Listing
October 2018

Ectopic Expression of Human Gene in ESCC Cell Line Using Retroviral System.

Avicenna J Med Biotechnol 2018 Apr-Jun;10(2):75-82

Human Genetic Division, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Cancer/Testis Antigens (CTAs) are a sub-group of tumor-associated antigens which are expressed normally in germ line cells and trophoblast, and aberrantly in a variety of malignancies. One of the most important CTAs is Developmental Pluripotency Associated-2(DPPA2) with unknown biological function. Considering the importance of in developmental events and cancer, preparing a suitable platform to analyze roles in the cells seems to be necessary.

Methods: In this study, the coding sequence of gene was amplified and cloned into the retroviral expression vector to produce recombinant retrovirus. The viral particles were transducted to Esophageal Squamous Cell Carcinoma (ESCC) cell line (KYSE-30 cells) and the stable transducted cells were confirmed for ectopic expression of gene by real-time PCR.

Results: According to the critical characteristics of retroviral expression system such as stable and long time expression of interested gene and also being safe due to deletion of retroviral pathogenic genes, this system was used to induce expression of gene and a valuable platform to analyze its biological function was prepared. Transduction results clearly showed efficient overexpression of the gene in target cells in protein level due to high level of GFP expression.

Conclusion: Such strategies can be used to produce high levels of desired protein in target cells as a therapeutic target. The produced recombinant cells may present a valuable platform to analyze the effect of ectopic expression in target cells. Moreover, the introduction of its potential capacity into the mouse model to evaluate the tumorigenesis of these cancer cells leads to an understanding of the biological importance of in tumorigenesis. In addition, our purified protein can be used in a mouse model to produce specific antibody developing a reliable detection of existence in any biological fluid through ELISA system.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960063PMC
June 2018

Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Asian Pac J Cancer Prev 2018 May 26;19(5):1313-1318. Epub 2018 May 26.

Department of Cellular and Molecular Biology, University of Science and Culture, Tehran, Iran.

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation and metastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) and previous studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, we tested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes in patients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixed paraffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 were studied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between single nucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existence of a significant relationship between tumor recurrence and overall survival was proved in this study, with at least one allele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These results provide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients. This result could help identify individuals with GC who have a high risk of tumor recurrence.
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031830PMC
May 2018

Isolation and identification of chemotherapy-enriched sphere-forming cells from a patient with gastric cancer.

J Cell Physiol 2018 10 10;233(10):7036-7046. Epub 2018 May 10.

Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient. Small subpopulation of dissociated cells after tissue digestion formed spheroid colonies in serum-free media under the non-adherent condition. These spheroid colonies differentiated into epithelial like cells in serum-containing medium. Few sphere-forming cells carried CD44 and CD54 markers overexpressed DLL4 that is responsible for tumor growth and angiogenesis. Subcutaneous injections of sphere-forming cells in different passages conferred tumorigenicity in nude mice. Sphere-forming cells upregulated CD44 polymorphisms CD44v3, -v6, and -v8 -10, stemness factors OCT4, SOX2, SALL4 and Cripto-1, self-renewal molecules IHh, Wnt, β-catenin and BMI1, and epithelial mesenchymal transition (EMT) markers Twist1 and Snail1 in vitro and in vivo. Moreover, these cells similar to sphere-forming cells isolated from a chemotherapy-free patient expressed Oct-4 and β-catenin proteins. However, the Twist1 protein was only expressed by sphere-forming cells derived from the chemotherapy-treated patient. Thus, these cells have all the characteristics of stationary and migratory CSCs, including tumorigenicity, self-renewal, pluripotency, invasion and metastasis. Taken together, targeting chemotherapy-enriched CSCs as chemo-resistance cells observed in GC patients can provide more effective therapeutic strategies compared to untreated patients.
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http://dx.doi.org/10.1002/jcp.26627DOI Listing
October 2018

Protective effect of thymoquinone, the main component of , against diazinon cardio-toxicity in rats.

Drug Chem Toxicol 2019 Nov 12;42(6):585-591. Epub 2018 Apr 12.

Department of Pharmacology and Toxicology, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran.

Several studies have shown that oxidative stress and cell damage can occur at very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of (black seed or black cumin), against DZN cardio-toxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups: control (corn oil gavages), DZN gavages (20 mg/kg/day), Thy gavages (10 mg/kg/day) and Thy + DVN gavages (2.5, 5 and 10 mg/kg/day). Treatments were continued for 28 days, then the animals were anesthetized by ether and superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), lactate dehydrogenize (LDH) and glutathione peroxide (GPX) activity was evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) the heart tissue and creatinephosphokinase-MB (CPK-MB) and troponin (TPI) levels and cholinesterase activity in the blood were evaluated. DZN-induced oxidative damage and elevated the levels of the cardiac markers CK-MB, TPI, MDA and LDH and decreased SOD, CAT and cholinesterase activity and GSH level compared with the control group. Treatment with Thy reduced DZN cardio-toxicity and cholinesterase activity. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Administration of Thy as a natural antioxidant decreased DZN cardio-toxicity and improved cholinesterase activity in rats through the mechanism of free radical scavenging.
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http://dx.doi.org/10.1080/01480545.2018.1454459DOI Listing
November 2019

Expression of p63 and CD44 in oral squamous cell carcinoma and correlation with clinicopathological parameters.

Arch Oral Biol 2017 Oct 15;82:160-165. Epub 2017 Jun 15.

Biostatistical Sciences Department, Mashhad University of Medical Sciences, Mashhad, Iran.

Squamous cell carcinoma (SCC) is the sixth most frequent malignant tumor of the head and neck region. Despite advances in therapeutic options over the last decades, the rate of mortality and morbidity has not been improved markedly. A small subset of cells, cancer stem cells (CSCs), with self-renewal properties have become a major focus of current cancer research. CD44 and p63 are identified as candidate stem cell markers in normal squamous epithelium and SCC. The role of these markers in oral squamous cell carcinoma (OSCC) is still debatable. The aim of this study was to evaluate immunohistochemical expression of these markers in OSCC samples and also correlates the expression of these markers with some clinicopathological parameters of prognostic significance including histological grading, TNM staging, overall survival (OS) rate as well as patients' age, gender, and tumor location. CD44 and p63 were expressed in all studied lesions with different degrees. Statistically significant difference was observed between CD44 and p63 expression with tumor grade and stage with higher expression in high grade and advanced OSCCs. No significant relationship was detected between markers immunoreactivity and patients age, gender, tumor location as well as OS. These markers can possibly advance our understanding of the initiating mechanisms and pathogenesis of OSCC and also result in novel therapeutic target in cancer treatment.
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http://dx.doi.org/10.1016/j.archoralbio.2017.06.011DOI Listing
October 2017

The prevalence and expression pattern of melanoma-associated antigen 1 in esophageal squamous cell carcinoma: a historical cohort study.

Electron Physician 2017 Feb 25;9(2):3756-3763. Epub 2017 Feb 25.

M.D., Student Research Committee, Department of Radiation Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Melanoma-associated antigen 1 (MAGE1) expression in normal tissues is restricted to the testes, whilst being over-expressed in a number of human cancers. This feature of MAGE1 makes it a promising cancer biomarker. This study aimed to determine the expression of MAGE1 in esophageal squamous cell carcinoma (SCC) and its relationship with clinicopathological factors.

Methods: This is a cross-sectional study conducted on pretreatment endoscopic tissue specimens of 43 patients with non-metastatic esophageal SCC, admitted to Omid Hospital, Mashhad, Iran, between 2011 and 2013. Out of 127 esophageal SCC patients who had already enrolled in a trial of trimodality therapy, we chose 43 patients whose paraffin blocks of endoscopic samples were accessible, which we then stained for MAGE1 expression by immunohistochemistry. Correlation of MAGE1expression and clinicopathological data (age, sex, stage, grade, and outcome) was assessed using SPSS 16 by T test, chi-square, and Pearson tests (p <0.05 was considered significant).

Results: MAGE1 was expressed in 46.5% (20 out of 43) of esophageal SCC specimens. The MAGE1 nuclear staining increased significantly by age; its expression for <40, 41-49, 50-59, 60-69, and ≥70 years old was 0%, 0%, 8.3%, 26.3%, and 100%, respectively (p=0.02; Person's R value = 0.3 and p=0.04). There was no significant correlation between MAGE1 expression and other clinicopathological parameters.

Conclusion: MAGE1 antigen has considerable expression in the esophageal SCC among the Iranian population; it can be potentially applied as a cancer biomarker as well as a target for immunotherapy in patients with esophageal SCC.
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http://dx.doi.org/10.19082/3756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410902PMC
February 2017

EGFR Expression in Patients with Esophageal Squamous Cell Carcinoma and its Association with Pathologic Response to Preoperative Chemoradiotherapy: A Study in Northeastern Iran.

Arch Iran Med 2017 Apr;20(4):240-245

Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all esophageal cancers worldwide. It is the most common histological type of esophageal carcinoma in low-resource countries. ESCC is prevalent in Asian countries, accounting for more than 95% of esophageal cancers. The epidermal growth factor receptor (EGFR) is involved in cancer development, as its gene is often mutated and/or amplified in cancer cells. According to recent statistics, esophageal cancer is the eighth most common cancer in Iran.

Methods: In this retrospective study, we assessed EGFR overexpression, using immunohistochemistry (IHC) in 68 patients with ESCC, undergoing neoadjuvant chemoradiotherapy and esophagectomy in 2011-2014. The treatment protocol included external beam radiotherapy (40 Gy), concomitant with cisplatin 20mg/m2 and 5- fluorouracil (5-FU) 1000 mg/m2 for 4 consecutive days during the first and fourth weeks of treatment. To compare the two groups (EGFR positive and negative) in terms of complete pathologic response, Chi-square test was performed using SPSS version 16.

Results: The median age of the patients was 59 years (range: 27-70 years), with a female-to-male ratio of 1.06. Overall, 70% of the subjects showed EGFR overexpression. Complete pathologic response to neoadjuvant treatment was significantly higher in EGFR-positive patients (40% vs. 15.8%, P = 0.05). In all cases, 1- and 3-year overall survival rates were 86.6% ± 4.1 and 48% ± 6.9, respectively. The 1- and 3-year disease free survival rates were calculated as 71.8% ± 5.4 and 44.3% ± 6.5, respectively. The overall survival rate was relatively higher in cases with EGFR overexpression, although the difference was not statistically significant (5-year survival rate: 47.9 ± 8.2 vs. 30.9 ± 13, P = 0.23).

Conclusion: EGFR overexpression was reported in the majority of patients with ESCC in northeastern Iran. Moreover, EGFR overexpression was significantly associated with complete pathologic response.
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http://dx.doi.org/0172004/AIM.0010DOI Listing
April 2017

 Evaluation of serum HBV viral load, transaminases and histological features in chronic HBeAg-negative hepatitis B patients.

Gastroenterol Hepatol Bed Bench 2017 ;10(1):39-43

Internal Medicine Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Aim: To evaluate the association between biochemical, virologic and histologic features in patients with HBeAg-negative chronic hepatitis B (CHB).

Background: Hepatitis-B e-antigen (HBeAg)-negative is common in Iran, is progressive with poor prognosis. Therefore, it seems necessary to perform a comprehensive evaluation of different spectrum of laboratory measurements accompanying histological findings.

Methods: HBeAg- negative CHB patients referring to two university hospitals during two years were enrolled. Alcohol consumption, liver mass, fatty liver and positive results of Anti HDV, Anti HCV or Anti HIV were excluded. The relationship between viral loads, liver enzymes (old and new cutoffs) and histopathological features was analyzed using descriptive and analytic statistical methods.

Results: A total of 150 HBeAg-negative CHB (males=110, mean age=38.44±11.34 years) were assessed. ALT had a significant relation with the logarithm of serum HBV-DNA (P<0.0001), grade and stage on liver biopsy (P<0.001, P=0.034, respectively). Serum viral load, AST and ALT were independent predictors of histological grade, age was the only independent predictor of the stage of liver fibrosis. There was a significant relationship between serum ALT and stage of liver fibrosis (P<0.0001) when new cutoff values for ALT were considered. We found that age had a significant relation with histological grade but it showed a reverse relation with ALT levels (P=0.009).

Conclusion: In HBeAg-negative CHB, AST had a better prediction for liver necrosis and inflammation. Age could be an independent predictor for liver fibrosis. New cutoff values for ALT had superiority over conventional values to identify higher risk of liver fibrosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346823PMC
January 2017

Expression analysis of matrix metalloproteinase-13 in human gastric cancer in the presence of Helicobacter Pylori infection.

Cancer Biomark 2017 ;18(4):349-356

Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Matrix metalloproteinases (MMPs) can degrade essentially the extracellular matrix (ECM) components. MMPs are important regulators of tumor growth; hence the enzymes are considered as important targets for cancer therapy. MMP-13 is specially activated in gastric cancer and promotes the invasiveness of the primary tumors. Helicobacter Pylori (H.pylori) interacts with gastric epithelial cells and stimulates it to produce MMP-13in vitro.

Objective: The relation between MMP-13 gene expression and clinicopathological characteristics of gastric cancer in the presence of H.pylori infection was investigated in fifty patients.

Methods: The level of MMP-13 gene expression was measured by quantitative Real-time PCR method and was evaluated between two groups of normal and carcinomatous tissues.

Results: The results showed 30% elevation of MMP-13 expression in tumor tissues. H.pylori infection did not have a significant effect on the expression of MMP-13. There was a correlation between gene expression and tumor type (P value = 0.032). In addition, there was a significant correlation between MMP-13 gene expression and tumor stage in intestinal group (P value = 0.023).

Conclusions: Based on the results, it might be concluded that in intestinal group, immune system plays an important role in reducing gene expression. Results also showed over expression (60%) in diffuse group. These findings suggest that using MMP-13 inhibitors in diffuse group might contribute to the control of tumor growth.
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http://dx.doi.org/10.3233/CBM-160127DOI Listing
March 2018

Cytokine networks and their association with Helicobacter pylori infection in gastric carcinoma.

J Cell Physiol 2018 04 7;233(4):2791-2803. Epub 2017 Mar 7.

Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Cytokine networks as dynamic networks are pivotal aspects of tumor immunology, especially in gastric cancer (GC), in which infection, inflammation, and antitumor immunity are key elements of disease progression. In this review, we describe functional roles of well-known GC-modulatory cytokines, highlight the functions of cytokines with more recently described roles in GC, and emphasize the therapeutic potential of targeting the complex cytokine milieu. We also focus on the role of Helicobacter pylori (HP)-induced inflammation in GC and discuss how HP-induced chronic inflammation can lead to the induction of stem cell hyperplasia, morphological changes in gastric mucosa and GC development.
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http://dx.doi.org/10.1002/jcp.25822DOI Listing
April 2018

Ventricular endomyocardial fibrosis in a pregnant female with Behçet's disease.

Asian Cardiovasc Thorac Ann 2018 Oct 9;26(8):619-621. Epub 2017 Jan 9.

5 Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran.

A 32-year-old pregnant woman, diagnosed with Behçet's disease 6 months earlier, presented with recent mild hemoptysis and exertional dyspnea. Transthoracic echocardiography showed an enlarged dysfunctional right ventricle. A large hypoechoic triangular-shaped mass was seen attached to the inner right ventricular wall, filling the cavity. No change in the size of the mass was noted after anticoagulant administration, and right heart failure progressed. Surgery was performed to remove the mass and repair the tricuspid valve. This was a very rare presentation of Behçet's disease in pregnancy, which resulted in delivery of a completely healthy baby despite corticosteroid pulse therapy and cyclophosphamide.
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http://dx.doi.org/10.1177/0218492316687177DOI Listing
October 2018

Resolution of Bile Duct Adenoma over Follow-up Period; A Case Report.

Middle East J Dig Dis 2016 Oct;8(4):327-330

Assistant Professor, Department of medical sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

Bile duct adenoma (BDA) is a rare neoplasm of bile ducts with various clinical manifestations and imaging appearances. A few cases of BDA and their predisposing factors have been described. We report a 35-year-old woman with right upper quadrant pain who consumed oral contraceptive pills. Ultrasound study revealed three hypoechoic subcapsular liver masses; two of them were hypodense in computed tomography. Fine needle biopsy of the largest mass showed bile duct adenoma. Liver masses disappeared after discontinuing the pills over a 2-year follow-up. BDAs can manifest in imaging. Although previous studies have not reported tumor resolution over a follow-up period, we suggest paying more attention to predisposing factors in order to give an opportunity for tumor resolution by risk factor elimination.
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http://dx.doi.org/10.15171/mejdd.2016.44DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5145302PMC
October 2016

Evaluation of MAGE-1 Cancer-Testis Antigen Expression in Invasive Breast Cancer and its Correlation with Prognostic Factors.

Iran J Cancer Prev 2016 Aug 15;9(4):e4404. Epub 2016 Aug 15.

Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IR Iran.

Background: Aberrant expression of cancer-testis antigens (CTA) in breast carcinoma tissue, and its natural expression in the testis, the tissue away from the immune system, makes them good candidates for cancer immunotherapy and vaccines designing.

Objectives: The aim of this study was to assess the expression of a CTA (MAGE-1) in invasive breast cancer and its correlation with prognostic factors.

Methods: Paraffin blocks of breast cancer tissues from 113 patients operated in 2011 - 2013 were stained for MAGE-1expression by immunohistochemistry (IHC). The associations of MAGE-1 expression with known prognostic factors were assessed by statistical analysis using SPSS 16.

Results: MAGE-1 expression was found in cancer cell cytoplasms of 30.1% of patients, with different degrees of intensity, (23.9% moderate and 6.2% strong). Nuclear staining turned positive in 31.8%, stratified from moderate in 26.5%to to strong in 5.3%. There was a significant association between the number of lymph nodes involved and both nuclear (P = 0.042) and cytoplasmic (P = 0.003) MAGE-1 expression. There was also a significant correlation between the nuclear expression of MAGE-1 and tumor size (P = 0.018). Cytoplasmic expression of MAGE-1 increased with increasing pathologic grade of tumors although the association was not statistically significant (P = 0.119).

Conclusions: CTA MAGE-1 has significant association with some prognostic factors in breast cancer and may have the role of a prognostic factor.
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http://dx.doi.org/10.17795/ijcp-4404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056020PMC
August 2016

Matrix Metalloproteinase-13 - A Potential Biomarker for Detection and Prognostic Assessment of Patients with Esophageal Squamous Cell Carcinoma.

Asian Pac J Cancer Prev 2016 ;17(6):2781-5

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran E-mail :

Background: Matric metalloproteinase (MMP) 13 gene expression is increased in esophageal squamous cell carcinomas (ESCCs) and associated with increasing tumor invasion, lymph node involvement and decreased survival rates. Levels of the circulating enzyme may be elevated and used as a marker of tumor progression. In this study, clinical application of MMP-13 serum levels was evaluated for early detection, prediction of prognosis and survival time of ESCC patients.

Materials And Methods: Serum levels of MMP13 were determined by ELISA in 66 ESCC patients prior of any treatment and 54 healthy controls for comparison with clinicopathological data through statistical analysis with Man Whitney U and Log-Rank tests. In addition, clinical value of MMP13 levels for diagnosis was evaluated by receiver operating characteristic (ROC) test.

Results: The serum level of MMP-13 in patients (>250 pg/ml) was significantly higher than in the control group (<100 pg/ml) (p value=0.004). Also the results showed a significant correlation between MMP-13 serum levels with tumor stage (p value = 0.003), depth of tumor invasion (p value=0.008), involvement of lymph nodes (p value = 0.011), tumor size (p value = 0.018) and survival time. While there were no significant correlation with grade and location of tumors. ROC analysis showed that MMP-13 level is an accurate diagnostic marker especially to differentiate pre-invasive/ invasive lesions from normal controls (sensitivity and specificity: 100%).

Conclusions: These findings indicate a potential clinical significance of serum MMP13 measurement for early detection and prognostic assessment in ESCC patients.
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January 2017

Primary Pulmonary Valve Leiomyosarcoma in a 35-Year-Old Woman.

Tex Heart Inst J 2016 Feb 1;43(1):84-7. Epub 2016 Feb 1.

Primary cardiac leiomyosarcomas are rare, with a high incidence of local recurrence. Herein, we report the case of a 35-year-old woman who was admitted with right ventricular failure and suspected pulmonary embolism. Upon echocardiography, we detected a mass in the pulmonary trunk that involved the pulmonary valve and led to valvular stenosis. The optimal protocol for treating these tumors is as yet unclear. Complete resection can rarely be achieved. However, palliative surgery is usually undertaken because many patients present with mechanical obstruction, such as significant pulmonary stenosis.
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http://dx.doi.org/10.14503/THIJ-14-4748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810595PMC
February 2016

Cardiac Involvement in Non-Hodgkin Lymphoma, an Incidental Large Atrial Mass: A Case Report.

Iran J Cancer Prev 2015 Oct 27;8(5):e3913. Epub 2015 Oct 27.

Department of Patholgy, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, IR Iran.

Introduction: Cardiac involvement as an initial presentation of malignant lymphoma has been a rare occurrence.

Case Presentation: We have reported a 78 year old man with complaint of abdominal pain and vomiting. In patients preoperative evaluation for surgical management of an intra-abdominal mass, a large intracardiac mass has found incidentally during the echocardiography. Pathologic biopsy of right atrial mass that has removed by open heart surgery shown: non Hodgkin-B cell lymphoma. Bone marrow biopsy was taken and was positive for lymphomatous involvement.

Conclusions: The patient has treated by CHOP chemotherapy regiment successfully and after completion of treatment, there was complete response.
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http://dx.doi.org/10.17795/ijcp-3913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667233PMC
October 2015

Safranal as a safe compound to mice immune system.

Avicenna J Phytomed 2015 Sep-Oct;5(5):441-9

Medical Toxicology Research Center and Pharmacy School, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: The aim of the present study was to investigate immunotoxic effect of safranal (SAF), a main component of Crocus sativus essential oil, using Balb/c mice.

Materials And Methods: SAF was administered intraperitoneally at doses of 0.1, 0.5 and 1 ml/kg for 3 weeks. Hystopathological examination of spleen and bone marrow, cellularity of spleen, delayed type of hypersensitivity (DTH) response, hemagglutination titer (HA), cytokine production and lymphocyte proliferation assay were studied in various groups of animals.

Results: Spleen cellularity for SAF groups (0.1 ml/kg SAF: 6.68 [± 0.88] × 10(7), 0.5 ml/kg SAF: 8.16 [± 1.33] × 10(7), 1 ml/kg SAF: 6.12 [± 0.59] × 10(7)) did not significantly differ as compared to vehicle control (8.52 [± 1.36] × 10(7); p > 0.05). In addition, SAF at all doses could not produce any significant changes in hematological parameters, HA titer, DTH and lymphoproliferation responses, as well as in release of cytokines by isolated splenocytes (p > 0.05). Despite a few studies demonstrating some immunomodulatory effects for saffron extract, SAF as a major constituent of saffron did not induce any marked effects in immune system parameters of mice.

Conclusion: Contrary to the toxicological studies which have indicated that SAF is more toxic than other active constituents in saffron stigma, at least it was found to be safe to mice immune system and has no toxicity on humoral and cellular immune responses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599109PMC
October 2015

Predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma.

Tumour Biol 2016 Feb 28;37(2):1715-25. Epub 2015 Aug 28.

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

The three amino acid loop extension (TALE) class myeloid ecotropic viral integration site 1 (MEIS1) homeobox gene is known to play a crucial role in normal and tumor development. In contrast with its well-described cancer stemness properties in hematopoietic cancers, little is known about its role in solid tumors like esophageal squamous cell carcinoma (ESCC). Here, we analyzed MEIS1 expression and its clinical relevance in ESCC patients and also investigated its correlation with the SOX2 self-renewal master transcription factor in the ESCC samples and in the KYSE-30 ESCC cell line. MEIS1 mRNA and protein expression were significantly decreased in ESCC disease (P < 0.05). The inverse correlation between MEIS1 mRNA expression and tumor cell metastasis to the lymph nodes (P = 0.004) was significant. Also, MEIS1 protein levels inversely correlated to lymph node involvement (P = 0.048) and high tumor stage (stages III/IV, P = 0.030). The low levels of DNA methylation in the MEIS1 promoter showed that this suppression does not depend on methylation. We showed that downregulation of EZH2 restored MEIS1 expression significantly. Also, we investigated that MEIS1 downregulation is concomitant with increased SOX2 expression. To the best of our knowledge, this is the first report on the MEIS1 gene in ESCC. The inverse correlation of MEIS1 with metastasis, tumor staging, and the role of EZH2 in methylation, together with its correlation with stemness factor SOX2 expression, led us to predict cancer stemness properties for MEIS1 in ESCC.
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http://dx.doi.org/10.1007/s13277-015-3780-9DOI Listing
February 2016

Immunotoxicity induced in mice by subacute exposure to berberine.

J Immunotoxicol 2016 23;13(2):255-62. Epub 2015 Jun 23.

c Medical Toxicology Research Center, School of Medicine .

The immunotoxic effects of the isoquinoline alkaloid berberine (BBR) were investigated in Balb/c mice. Here, BBR was administered daily by intraperitoneal injection at doses of 5 and 10 mg/kg for 14 days. Following the exposure, host spleen weight, cellularity and histopathology, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), spleen cell subtype profiles, splenocyte cytokine production and lymphocyte proliferation were studied in all of the test groups of animals. The results showed that the high dose of BBR (10 mg/kg) could suppress both cellular and humoral immune functions in the treated hosts. BBR at 5 mg/kg only appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that BBR has effective immunosuppressive properties. Mechanistic studies are required to determine exactly how this material is acting to impart many of the immunotoxic effects demonstrated here. At the same time, further research should also be performed on BBR to further develop its potential use as an effective immunosuppressant or co-adjuvant for the treatment of diseases caused by an exaggerated or unwanted immune response.
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http://dx.doi.org/10.3109/1547691X.2015.1058306DOI Listing
September 2016
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