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Razmkhah M.,Shiraz Institute for Cancer Research | Abedi N.,Shiraz Institute for Cancer Research | Hosseini A.,Shiraz Institute for Cancer Research | Ghaderi A.,Shiraz Institute for Cancer Research | Ghaderi A.,Shiraz University of Medical Sciences
Iranian Journal of Immunology | Year: 2015

Background: Adipose derived stem cells (ASCs) provoke the accumulation and expansion of regulatory T cells, leading to the modulation of immune responses in tumor microenvironment. Objective: To assess the effect of tumoral ASCs on the trend of regulatory T cells differentiation. Methods: Peripheral blood naïve CD4+ T cells were co-cultured with ASCs derived from breast cancer or normal breast tissues. In separate cultures peripheral blood naïve CD4+ T cells were exposed to the culture supernatants of ASCs. Results: Generation of CD4+CD25+Foxp3+ and CD4+CD25- Foxp3+ Treg subsets was observed after coculture of naïve CD4+ T cell with either ASCs or the related supernatant. The percentage of CD4+CD25+Foxp3+ cells increased after exposing naïve CD4+ T cells to both ASCs and their supernatants while augmentation of CD4+CD25-Foxp3+ subset mostly depended on the presence of ASCs. Similarly, upregulation of FoxP3 molecule was more significant in condition of cell to cell contact. IL-4 and IL-10 were up-regulated in the cocultured naïve CD4+ T cells after exposure to ASCs/supernatant while IFN-γ was down-regulated in the presence of ASCs. Conclusion: Accordingly, ASC may act as one of the major players in tumor site with immunomodulatory effects, which may mostly be carried out through direct cellcell interaction. © 2015, Shiraz University of Medical Sciences .All Rights Reserved.


Erfani N.,Shiraz Institute for Cancer Research | Rezaeifard S.,Shiraz Institute for Cancer Research | Haghshenas M.,Shiraz Institute for Cancer Research | Rasouli M.,Shiraz University of Medical Sciences
Iranian Journal of Immunology | Year: 2014

Background: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4+CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. Objectives: To investigate the percentage of CD4+CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women and to evaluate the correlation of the Treg cell percentage with clinicopathological characteristics including cancer stage and CA-125 serum level. Methods: Seventeen women with epithelial ovarian cancer and 20 healthy subjects were enrolled in the study. Peripheral blood mononuclear cells were stained at the surface, for CD4 and CD25 molecules, followed by fixation, permeabilization and intracellular staining for FoxP3 molecule. After processing and flowcytometry analysis, prevalence of Treg cells was determined as the percentages of CD25+FoxP3+ cells among CD4+ lymphocytes. Results: Despite no difference in the percentage of total CD4+ lymphocytes, analysis indicated that Treg cell percentage was significantly higher in ovarian cancer patients than controls (5.7 ± 3.1% versus 2.8 ± 1.4%, p=0.002). A trend toward higher Treg cells was observed in higher stages of ovarian cancer (III+IV) in comparison to lower stages (I+II) (6.5 ± 3.2% vs. 4.44 ± 2.7%, p=0.2). Higher percentage of Treg cells was also observed in the patients with high CA125 (CA-125 >100 U/mL) in comparison to those with low CA-125 serum level (CA-125 ≤ 100 U/mL) although the difference was not significant (6.44 versus 4.18%, p=0.19). Conclusion: Increased frequency of Tregs in ovarian cancer might participate in immune suppression in these patients. The findings collectively suggest the likely impact of Treg cell–targeted immunotherapy in ovarian cancer. © 2014, Shiraz University of Medical Sciences.


Rafnar T.,DeCODE Genetics Inc. | Vermeulen S.H.,Biostatistics and HTA | Sulem P.,DeCODE Genetics Inc. | Thorleifsson G.,DeCODE Genetics Inc. | And 76 more authors.
Human Molecular Genetics | Year: 2011

Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 3 10 -11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC. © The Author 2011. Published by Oxford University Press. All rights reserved.


PubMed | Shiraz University of Medical Sciences, Medicinal Plants Processing Research Center and Shiraz Institute for Cancer Research
Type: Journal Article | Journal: Pharmacognosy research | Year: 2015

Seaweeds have proven to be a promising natural source of bioactive metabolites for drug development.This study aimed to monitor the ethanol extract of ten algae from the Persian Gulf and Oman Sea, for their in vitro cytotoxic activity on three human breast cancer cell lines.Three human breast cancer cell lines including MDA-MB-231(ER(-)), MCF-7(ER(+)), and T-47D (ER(+)) were treated by different concentrations of total ethanol (90%) algae extracts and the cytotoxic effects were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Doxorubicin (Ebewe, Austria) was used as a positive control. After 72 h of incubation, the cytotoxic effect of the algae was calculated and presented as 50%-inhibitory concentration (IC50).The results indicated Gracilaria foliifera and Cladophoropsis sp. to be the most active algae in terms of cytotoxic effects on the investigated cancer cell lines. The IC50 values against MDA-MB-231, MCF-7, and T-47D cells were, respectively, 74.89 21.71, 207.81 12.07, and 203.25 30.98 g/ml for G. foliifera and 66.48 4.96, 150.86 51.56 and >400 g/ml for Cladophoropsis sp. The rest of the algal extracts were observed not to have significant cytotoxic effects in the concentration range from 6.25 g/ml to 400 g/ml.Our data conclusively suggest that G. foliifera and Cladophoropsis sp. may be good candidates for further fractionation to obtain novel anticancer substances. Moreover, stronger cytotoxic effects on estrogen negative breast cancer cell line (MDA-MB-231(ER(-))) in comparison to estrogen positive cells (MCF-7 and T-47D) suggest that the extract of G. foliifera and Cladophoropsis sp. may have an estrogen receptor/progesterone receptor-independent mechanism for their cellular growth inhibition.


Moghanibashi M.,Islamic Azad University | Mohamadynejad P.,Islamic Azad University | Rasekhi M.,Islamic Azad University | Ghaderi A.,Shiraz Institute for Cancer Research | Mohammadianpanah M.,Shiraz University of Medical Sciences
Gene | Year: 2012

TFF1 is a cysteine-rich protein that forms a characteristic trefoil domain through disulfide bonds, which render it resistant to vigorous conditions and it involves in maintaining the integrity of the gastric mucosa. Decreased expression of TFF1 gene plays a role in the development of gastric cancer. We examined the association between the promoter polymorphisms of the TFF1 gene and the risk of development of gastric cancer, in a case-control study including 199 controls and 141 patients with gastric cancer. Assessment of single nucleotide polymorphisms in the promoter region of the TFF1 gene was performed by sequencing and polymerase chain reaction-based restriction fragment length polymorphism. We found a statistically significant increased risk of gastric cancer associated with - 394 TT genotypes (OR = 8.78, CI = 2.85-27.05, p < 0.001) and CT (OR = 1.64, CI = 1.04-2.60, p = 0.033). This single nucleotide polymorphism occurs naturally in an estrogen response element. According to induction of the TFF1 gene by estrogen, it is possible that the substitution of C to T results in a decreased estrogen receptor binding affinity to the estrogen response element and in turn it decreases the expression of the TFF1 gene that may be involved in development of gastric cancer over a lifetime. © 2011 Elsevier B.V.


Andisheh-Tadbir A.,Oral and Dental Health Care Research Center | Khademi B.,Khalili Hospital | Malekzadeh M.,Shiraz Institute for Cancer Research | Zareifar B.,Shiraz University of Medical Sciences
Journal of Biological Sciences | Year: 2014

Monocyte chemoattractant protein-1 (MCP-1) has been shown to be a potent chemotactic factor for monocytes. It acts as an important factor in the cytokine network which regulates tumor proliferation. The association between serum MCP-1 level and oral squamous cell carcinoma has not been clarified yet. The aim of this study was to determine MCP-1 serum levels in patients with oral squamous cell carcinoma and investigate if it is correlated with clinicopathological features of tumor. Using an ELISA kit, the circulating levels of MCP-1 in blood serum of 54 oral squamous cell carcinoma patients with 32 healthy control samples were assessed. The serum MCP-1 concentration in OSCC patients was significantly lower (573.1±238.6 pg mL-1, n = 54) compared with healthy controls (719.7±354.5 pg mL-1, n = 32; p = 0.02). There was no apparent correlation in serum MCP-1 concentration with the clinicopathological features such as stage, tumor size, nodal status and histological grade. Serum levels of MCP-1 decreased in patients with oral squamous cell carcinoma but no clear-cut relationship was detected between MCP-1 levels and clinicopathologic factor. These results suggest that MCP-1 may not be a useful marker for recognition of clinical behavior of oral squamous cell carcinoma but further studies is recomended. © 2014 Asian Network for Scientific Information.


Jaberipour M.,Shiraz Institute for Cancer Research | Habibagahi M.,Immunotherapy Laboratory | Hosseini A.,Shiraz Institute for Cancer Research | Abbasi M.,Shiraz Institute for Cancer Research | And 4 more authors.
Indian Journal of Cancer | Year: 2010

Background: Proteins encoded by FAS, BCL-2 and TP53 genes are major regulators of cellular survival and apoptosis. Results of recent investigations show remarkable biological features of these factors, which propose their role in the course of cancer. Therefore, it is plausible to test whether transcripts of these genes could be detected in the peripheral blood cells of patients with breast cancer. Materials and Methods: Real-time polymerase chain reaction assay was performed to detect FAS, BCL-2, and TP53 gene transcripts in the peripheral blood samples of 50 women with histologically confirmed infiltrative ductal carcinoma of the breast. Gene expression of patients was compared with 40 healthy women without history of malignancies or autoimmune disorders. Results: The relative overexpression of BCL-2 in the blood cells from patients of early stages (I and II), nonmetastatic and low-grade tumors compared with healthy individuals, was shown by measuring the gene transcript. Similarly, 3-4-fold higher expression of FAS was found in those patients. The measurement of TP53 transcripts also showed higher levels of gene expression in patients compared with healthy controls. BCL-2 gene expression showed a significant correlation with FAS, while such a correlation was not observed between BCL-2 and TP53. Conclusion: It seems tumor cells overexpress BCL-2 to inhibit apoptosis and guarantee their cell survival. As a physiologic response, FAS and TP53 could be upregulated to suppress tumors. However, these pathways at early stages of disease may be inadequate and cause progressive malignancy.


Ansari M.,Shiraz University of Medical Sciences | Porouhan P.,Shiraz University of Medical Sciences | Mohammadianpanah M.,Shiraz Institute for Cancer Research | Omidvari S.,Shiraz University of Medical Sciences | And 4 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2016

Nausea and vomiting are among the most serious side effects of chemotherapy, in some cases leading to treatment interruption or chemotherapy dose reduction. Ginger has long been known as an antiemetic drug, used for conditions such as motion sickness, nausea-vomiting in pregnancy, and post-operation side effects. One hundred and fifty female patients with breast cancer entered this prospective study and were randomized to receive ginger (500 mg ginger powder, twice a day for 3 days) or placebo. One hundred and nineteen patients completed the study: 57 of them received ginger and 62 received ginger for the first 3 chemotherapy cycles. Mean age in all patients was 48.6 (25-79) years. After 1st chemotherapy, mean nausea in the ginger and control arms were 1.36 (±1.31) and 1.46 (±1.28) with no statistically significant difference. After the 2nd chemotherapy session, nausea score was slightly more in the ginger group (1.36 versus 1.32). After 3rd chemotherapy, mean nausea severity in control group was less than ginger group [1.37 (±1.14), versus 1.42 (±1.30)]. Considering all patients, nausea was slightly more severe in ginger arm. In ginger arm mean nausea score was 1.42 (±0.96) and in control arm it was 1.40 (±0.92). Mean vomiting scores after chemotherapy in ginger arm were 0.719 (±1.03), 0.68 (±1.00) and 0.77 (± 1.18). In control arm, mean vomiting was 0.983 (± 1.23), 1.03 (± 1.22) and 1.15 (±1.27). In all sessions, ginger decreased vomiting severity from 1.4 (±1.04) to 0.71 (±0.86). None of the differences were significant. In those patients who received the AC regimen, vomiting was less severe (0.64 ± 0.87) comparing to those who received placebo (1.13±1.12), which was statistically significant (p-Value < 0.05). Further and larger studies are needed to draw conclusions.


Faghih Z.,Shiraz Institute for Cancer Research | Rezaeifard S.,Shiraz Institute for Cancer Research | Safaei A.,Shiraz University of Medical Sciences | Ghaderi A.,Shiraz Institute for Cancer Research | Erfani N.,Shiraz Institute for Cancer Research
Iranian Journal of Immunology | Year: 2013

Background: CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. Objective: To evaluate the percentages of CD8+ lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes (TDLNs) of patients with breast cancer. Methods: Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes (Tc1, Tc2 and Tc17) were quantified in CD8+ T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. Results: The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma (IDC), the mean expression of IFN-γ by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages (p=0.018 and p=0.009, respectively). Conclusion: As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages (Tc2 and Tc17) in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-γ by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.

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