Ahana Roy; Aitijhya Ghosh; Kasturi Sinha; Basundhara Mitra; Sudeshna Rakshit; Melvin George; Koustav Sarkar
Abstract
Background: Breast cancer is an uncontrolled growth of epithelial cells. The loss of BRCA1 activity due to mutation or down-regulation of gene expression promotes tumorigenesis and increases the risk of breast cancer. Objectives: Our aim was to pulsate lymphocytes of breast cancer patients and normal ...
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Background: Breast cancer is an uncontrolled growth of epithelial cells. The loss of BRCA1 activity due to mutation or down-regulation of gene expression promotes tumorigenesis and increases the risk of breast cancer. Objectives: Our aim was to pulsate lymphocytes of breast cancer patients and normal individuals, using Diospyros peregrina fruit preparation (DFP) to study the cancer protective immunity, and the signal transduction processes involved with it. We also investigated the role of DFP in the release of lymphocytic nitric oxide (NO), which is a key tumoricidal agent, known to regulate T-cell proliferation, cytokine production, cell signaling, and apoptosis. Methods: Using Ficoll-Hypaque gradient centrifugation, lymphocytes were isolated from the blood of 12 patients and 12 normal individuals. Cells were treated with or without DFP (2.5 µg/ml) for 48 hours. Both non-stimulated and stimulated cells were then subjected to MTT assay and NO release assay; following which qPCR was performed to estimate mRNA levels and percentage enrichment of certain genes. Results: DFP stimulates lymphocytic proliferation(p=0.0118) and release of NO(p=0.01) significantly.DFP also noticeablyenhances the expression of T helper (TH) cell 1 specific IFNG, IL12, TBX21 and signal transducer and activator of transcription 1 (STAT1) genes. DFP treatment significantly increases tumor protective immunity by decreasing the expression levels of TH2 network specific GATA3 and IL4 genes but increasing the expression levels of TH1 network specific IFNG, IL12, TBX21 and STAT1 genes. Conclusion: DFP increases the expression levels TH1 specific network genes which in turn help in evoking tumor protective immunity.
Asmaa M. Zahran; Asmaa S. Shaltout; Hussein Fakhry; Ola N. Abdel Fattah; Doaa F. Temerik; Salah M. Khalaf; Amal Rayan
Abstract
Background: It has been suggested that routine assessment and quantification of different lymphocyte subsets can provide clinically meaningful prognostic information in breast cancer (BC). Objective: To determine the relationship between peripheral blood lymphocyte subsets and pathological parameters ...
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Background: It has been suggested that routine assessment and quantification of different lymphocyte subsets can provide clinically meaningful prognostic information in breast cancer (BC). Objective: To determine the relationship between peripheral blood lymphocyte subsets and pathological parameters and response to therapy in patients with BC. Methods: Thirty patients with operable breast cancer treated surgically with either modified radical mastectomy or breast conservative surgery, and 20 healthy controls were included. For detection of lymphocyte subsets in peripheral blood; Fluorochrome-labeled monoclonal antibodies were used and cells were analyzed by flow cytometry. Patients were treated with chemotherapy, radiotherapy and hormonal treatment, and followed up to determine relapse and recurrence-free survival (RFS). Results: Significant differences were found in the frequencies of B, T, NK, NKT, and CD28‒T cells between patients with BC and controls. Moreover, a significant difference was found in the percentage of CD8+CD28‒ T cells between patients with different pathologic subtypes of BC and negative correlations were observed between the frequency of CD8+CD28‒T cells and memory B cells, and RFS. Also, a significant difference in the frequency of naïve B cells was found in patients with different tumor grades and a negative correlation was found between the frequencies of B cells and NKT cells. Conclusion: NK, NKT, lymphocytes, and CD28‒ T cells significantly differed between healthy controls and BC patients. Also, memory B cells were associated with good response to treatment while CD28‒ T cells were associated with shorter RFS.
Somayeh Rezaeifard; Akbar Safaei; Abdolrasoul Talei; Zahra Faghih; Nasrollah Erfani
Abstract
Background: NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. Objective: To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as ...
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Background: NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. Objective: To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as activated T lymphocytes, in tumor draining lymph nodes (TDLNs) of patients with breast cancer (BC) and their association with different clinic-pathological features of the patients. Methods: Axillary lymph nodes were obtained from 30 Iranian women with breast cancer. After routine pathological evaluations, mononuclear cells were separated from their lymph nodes and incubated with appropriate fluorochrome conjugated monoclonal antibodies specific for CD3, HLA-DR, CD16/56, and Vα24Jα18-TCR. Data were collected on a four-color flow cytometer and analyzed by CellQuest software. Results: The mean percentages of NK (CD3-CD16/56+), NKT (CD3+CD16/56+) and iNKT (Vα24Jα18-TCR+) cells in TDLNs mononuclear cells of BC patients were 2.04%, 2.44% and 0.1%, respectively. A significant decrease in the percentages of NK and iNKT subsets in patients with grade I was observed compared to grade III (p=0.03 and p=0.01, respectively). Moreover, NK cells were increased in patients with grade III of BC compared to grade II (p= 0.003). Conclusion: The increase in the percentage of NK and iNKT cells in TDLNs of patients with higher grade of BC might suggest a suppressive phenotype for these cells in breast cancer, which merit more functional investigation.
Mohsen Arabpour; Atri Ghods; Mahmoud Shariat; Abodl-Rasoul Talei; Fereshteh Mehdipour; Abbas Ghaderi
Abstract
Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: ...
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Background: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity. Objective: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters. Methods: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry. Results: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage. Conclusions: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.
Reza Hosseini-Ghatar; Tahereh Soltantoyeh; Motahareh Bahadori; Jalal Khoshnoodi; Forough Golsaz-Shirazi; Mahmood Jeddi-Tehrani; Mohammad Mehdi Amiri; Fazel Shokri
Volume 14, Issue 3 , September 2017, , Pages 200-214
Abstract
Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously ...
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Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. Objective: To employ recombinant eukaryotic HER2-ECD subdomains to raise anti-HER2 antibodies and determine their anti-tumor activity in vitro. Methods: Two paired subdomains of HER2-ECD (DI+II and DIII+IV), representing Pertuzumab and Trastuzumab binding domains, respectively, along with the full extracellular domain of HER2 were generated in CHO-K1 cells. Polyclonal antibodies were raised against these subdomains and characterized using ELISA, flow cytometry, and immunoblot and their anti-tumor activity was assessed by XTT assay. The cross-reactivity of these antibodies was specified along with other members of the human HER family. Results: Similar to Trastuzumab and anti-HER2-ECD antibody, anti-DI+II and DIII+IV polyclonal antibodies reacted with recombinant HER2-ECD and native HER2 expressed on tumor cells. These two polyclonal antibodies were able to inhibit the binding of Pertuzumab and Trastuzumab to HER2, respectively, and did not cross-react with other members of HER family. These antibodies were able to inhibit tumor cell growth in vitro, similar to Trastuzumab. Conclusion: The high immunogenicity of human HER2 DI+II and DIII+IV subdomains in rabbits and the tumor inhibitory activity of the purified specific antibodies imply that they might be suitable for active immunotherapy in formulation with appropriate adjuvants and in combination with other HER2 specific therapeutics.
Fateme Sadri-Ardalani; Moslem Ahmadi; Azam Hemmati; Shaghayegh Emami; Samira Farid; Mohammad Mehdi Amiri; Mahmood Jeddi-Tehrani; Mahdi Shabani; Fazel Shokri
Volume 14, Issue 2 , June 2017, , Pages 99-110
Abstract
Background: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 ...
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Background: In addition to passive immunotherapy using anti-HER2 monoclonal antibodies, active immunotherapy via HER2 targeting is an interesting approach to inducing specific anti-tumor immune responses. We have recently reported the immunogenicity of HER2 subdomains following DNA immunization and HER2 protein boosting. In the present study, we evaluated the immunogenicity of different HER2 extracellular subdomains for the induction of anti-HER2 antibody response in BALB/c mice. Objective: To investigate and characterize antibody responses to human recombinant proteins of HER2 extracellular subdomains in immunized mice. Methods: Four subdomains of HER2 extracellular domain were expressed in E.coli; subsequently, purified recombinant proteins were intraperitoneally injected in BALB/c mice with Freund's adjuvant. The anti-HER2 antibody response was detected by ELISA, immunoblotting and flow cytometry. Results: All the four HER2 subdomains along with the full extracellular domain (fECD) were able to induce specific anti-HER2 antibodies. Although anti-HER2 subdomains antibodies could not react with eukaryotic recombinant fECD protein by ELISA, they were able to recognize this protein by immunoblotting under both reduced and non-reduced conditions. Furthermore, only the sera of mice immunized with fECD protein could recognize native HER2 on HER2 overexpressing tumor cells (>99%) by flow cytometry. Moreover, fECD immunized mice sera inhibited the proliferation of tumor cells by XTT assay. Conclusion: The prokaryotic recombinant proteins of HER2 extracellular subdomains are immunogenic, yet the induced specific antibodies do not react with the native HER2 protein due to the paucity of post-translation modifications and /or distortion of the native conformation of isolated HER2 extracellular subdomains which might be potentially effective for induction of cell mediated immune response against HER2.
Mohammad Hasan Bargostavan; Gilda Eslami; Nasrin Esfandiari; Ali Shams Shahemabadi
Volume 13, Issue 1 , March 2016, , Pages 45-53
Abstract
Background: The role of Matrix Metalloproteinase 9 (MMP9) in tumor invasion and progression is prominent. A single nucleotide polymorphism (SNP) in the promoter region of MMP9 (-1562 C/T) increases the transcription and expression of this gene. On the other hand, MHC class I chain-related protein A and ...
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Background: The role of Matrix Metalloproteinase 9 (MMP9) in tumor invasion and progression is prominent. A single nucleotide polymorphism (SNP) in the promoter region of MMP9 (-1562 C/T) increases the transcription and expression of this gene. On the other hand, MHC class I chain-related protein A and B (MICA/B) in soluble forms may impair tumor immunogenicity by reducing Natural Killer Group 2D (NKG2D) densities on NK cells and MMP9 enzyme activity has a prominent role in shedding of MICA/B. Objectives: To investigate the association between MMP9 (-1562 C/T) polymorphism and serum MICA/B level in breast cancer patients. Methods: In this case-control study, 105 patients with breast cancer and 100 healthy age-matched women were selected from Yazd hospitals, Iran. The polymorphism of MMP9 (-1562 C/T) was determined by PCR-RFLP. Concentration of MICB and MICA in the sera of breast cancer patients and healthy women were measured using ELISA method. Results: The frequency of CC, CT and TT genotypes and T allele of the MMP9 (-1562 C/T) did not show significant differences between breast cancer patients and healthy donors (p>0.05). On the other hand, the mean serum levels of MICB and MICA were significantly elevated in patients compared with healthy individuals (p<0.05). In patients with MMP9CC genotype, the mean serum MICB concentration was significantly higher than those patients with CT polymorphism (p<0.05). Although the mean of blood MICA concentration in patients with the CT genotype was higher than those patients with CC genotype, the difference was not statistically significant. Conclusion: The T allele of the MMP9 (-1562 C/T) does not show a correlation with serum levels of MICA and MICB in breast cancer patients.
Ladan Langroudi; Zuhair Muhammad Hassan; Masoud Soleimani; Seyed Mahmoud Hashemi
Volume 12, Issue 4 , December 2015, , Pages 226-239
Abstract
Background: Differentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells. ...
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Background: Differentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells. Objective: To characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (T-MSCs) isolated from mammary tumors of BALB/c mice. Methods: Immunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Realtime PCR, respectively. Results: T-MSCs expressed significantly higher levels of HLADR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in TMSCs (p=0.07 and p=0.00, respectively). Additionally, T-MSCs expressed higher levels of iNOS and MMP9 (p=0.01 and p=0.01, respectively). T-MSCs were also able to induce higher levels of proliferation and migration of HUVEC endothelial cells in wound scratch assay compared to AD-MSCs (p=0.015). Conclusion: Functional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.
Mahboobeh Razmkhah; Nadieh Abedi; Ahmad Hosseini; Mohammad Taghi Imani; Abdol-Rasoul Talei; Abbas Ghaderi
Volume 12, Issue 1 , March 2015, , Pages 1-15
Abstract
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 ...
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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.
Zahra Faghih; Somayeh Rezaeifard; Akbar Safaei; Abbas Ghaderi; Nasrollah Erfani
Volume 10, Issue 4 , December 2013, , Pages 193-204
Abstract
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: ...
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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.
Maryam Azimi Mohamadabadi; Zuhair Mohammad Hassan; Ahmad Zavaran Hosseini; Mehrdad Gholamzad; Shekoofe Noori; Mehdi Mahdavi; Hamidreza Maroof
Volume 10, Issue 3 , September 2013, , Pages 139-149
Abstract
Background: Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells. Objective: To investigate the cytotoxic ...
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Background: Chemo-immunotherapy is one of the new achievements for treatment of cancer, by which the success of anti-cancer therapy can be increased. In vitro studies have been shown that Arteether (ARE) induces apoptosis in tumor cells, but not in normal cells. Objective: To investigate the cytotoxic and immunomodulatory properties of Arteether in-vivo and in-vitro. Methods: In this study, we used MTT assay for evaluation of cytotoxicity of Arteether on tumor cell line and Peripheral Blood Mononuclear Cells (PBMCs) from healthy individuals. Balb/c mice were subcutaneously transplanted with tumor tissue taken from Spontaneous Mouse Mammary Tumor (SMMT) bearing female mice. Arteether was administered to breast tumor-bearing Balb/c mice at a dose of 6 mg/kg/day intraperitoneally. Tumor sizes, lymphocyte proliferation, cytokines production, and the percentage of splenic T-reg cells were measured. Results: We observed that ARE could reduce the cell growth of 4T1 cell line in a dose-dependent manner but it had no cytotoxic effect on the growth of peripheral blood lymphocytes. ARE administered intraperitoneally to tumor-bearing Balb/c mice could reduce the tumor growth rate and splenic T-reg cells. No difference in the IFN-γ, IL-10 and IL-4 production was observed between tumor antigenstimulated splenocytes of mice treated with ARE and control mice. Conclusion: These results underscore antitumor properties of Arteether that may aid in development of more effective antitumor agents.
Maryam Hamidinia; Mehri Ghafourian Boroujernia; Abdolhassan Talaiezadeh; Ghasem Solgi; Maryam Taghdiri; Ali Khodadadi
Volume 10, Issue 1 , March 2013, , Pages 22-30
Abstract
Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: ...
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Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with breast cancer. Methods: Blood samples from 40 women with histologically-confirmed infiltrating ductal carcinoma of the breast and 40 healthy volunteer women without a history of malignancy or autoimmune disorders were collected. The abundance of FOXP3 and OX40 gene transcripts were determined by quantitative real-time PCR (qRT-PCR). Results: There was a significant positive correlation between FOXP3 and OX40 gene expression in women with breast cancer in a stage dependent manner. Conclusion: This finding emphasizes the importance of T-regs as predominant targets for breast cancer immunotherapy.
Nasrollah Erfani; Faezeh Moghaddasi-Sani; Mahboubeh Razmkhah; Mohammad Reza Haghshenas; Abdolrasoul Talaei; Abbas Ghaderi
Volume 9, Issue 4 , December 2012, , Pages 226-233
Abstract
Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known ...
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Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 agematched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.
Mehrnoosh Doroudchi; Abdolrasoul Talei; Helmout Modjtahedi; Alamtaj Samsami Dehaghani; Abdol Mohammad Pezeshki; Hilary Thomas; Abbas Ghaderi
Volume 2, Issue 4 , December 2005, , Pages 191-200
Abstract
Background: A soluble form of HER-2/neu extracellular domain (sHER-2) is reported to be released in the sera of metastatic breast cancer patients. Objective: To measure the level of sHER-2 in sera of 115 breast cancer patients. Methods: Serial samples of 27 patients with metastasis, 18 non-metastatic ...
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Background: A soluble form of HER-2/neu extracellular domain (sHER-2) is reported to be released in the sera of metastatic breast cancer patients. Objective: To measure the level of sHER-2 in sera of 115 breast cancer patients. Methods: Serial samples of 27 patients with metastasis, 18 non-metastatic patients, 15 patients in stage 0/I and 14 patients with accompanying benign breast disease were also included in this study. Results: No significant difference was observed between sHER- 2 level in the pre-operative sera of breast cancer patients and that of healthy individuals. Only 8 out of 27 patients whom later developed metastasis showed elevated levels of sHER-2 in their first serum sample. However, a trend of increase in the level of sHER-2 was observed in 14 (51.8%) of 27 metastatic sera before clinical diagnosis of the metastasis. A significant association between sHER-2 positive status and vascular invasion of the tumor was observed (P = 0.02). In addition, significant correlation of sHER-2 level with CEA (highest r = 0.74) and CA 15.3 (highest r = 0.74) tumor marker levels in the serial sera were observed. The mean time from sHER-2 positivity to tumor metastasis was calculated to be 98 days (range = 29-174). Conclusion: Our results indicate that a relatively high percentage of Iranian patients with breast cancer show an elevated level of sHER-2 in their sera before clinical diagnosis of the tumor metastasis. Therefore, measuring the level of this oncoprotein, not only helps physicians in monitoring the patients during HERCEPTINTM therapy, but also can be helpful in choosing more aggressive treatments at the early satges of tumor metastasis.
Sousan Farazmand; Dawar Amani; Zohair-Mohammad Hassan
Volume 2, Issue 3 , September 2005, , Pages 152-157
Abstract
Background: Alteration in peripheral blood lymphocytes (PBLs) is usually investigated to provide an evidence of the host immune responses to tumor antigens. The tumor infiltrating NK cells interact most closely with the tumor cells and more accurately reflect tumor host interactions. Objective: To analyze ...
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Background: Alteration in peripheral blood lymphocytes (PBLs) is usually investigated to provide an evidence of the host immune responses to tumor antigens. The tumor infiltrating NK cells interact most closely with the tumor cells and more accurately reflect tumor host interactions. Objective: To analyze peripheral blood and tumor associated Natural Killer (NK) cells in patients with breast cancer by immunophenotyping. Methods: Twenty women suffering from breast cancer were examined; 12 of them were confirmed histologically to be invasive ductal carcinoma. PBL and tissue samples from patients and matched control group were processed for analysis by flow cytometry. Results: Results of PBL analysis indicated a significant (P<0.05) increase in both the total number and activated NK cells in invasive ducal carcinoma patients compared to normal controls. No significant differences were noticed in the percent of NK cells and their activation marker expression in intra tumor lesion of the invasive ductal carcinoma and other tumors compared to benign lesions, however a decrease in the total NK number and activated NK cells was observed with progression of the tumor. Conclusion: Data of this investigation conclude that the total and activated NK cell number increase in peripheral blood of patients with breast cancer. The relationship between peripheral blood and intratumor NK cells needs more clarification, however, a decrease in intratumor NK cell number and their activation status occurs with tumor progression.
Hossein Abdolrahim-Zadeh; Niloufar Hakkakian; Reza Asadollahi; Behrouz Gharesifard; Jamal Sarvari; Eskandar Kamali-Sarvestani; Abdolrasoul Talei
Volume 2, Issue 3 , September 2005, , Pages 158-165
Abstract
Background: IL-10 is an anti-inflammatory cytokine which is involved in tumorigenesis. Over production of IL-10 and elevated number of IL-10 generating mononuclear cells in breast tumor tissue has already been shown. Objective: To determine the association of IL-10 promoter polymorphisms with increased ...
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Background: IL-10 is an anti-inflammatory cytokine which is involved in tumorigenesis. Over production of IL-10 and elevated number of IL-10 generating mononuclear cells in breast tumor tissue has already been shown. Objective: To determine the association of IL-10 promoter polymorphisms with increased risk of breast cancer and its association with breast cancer prognostic factors. Methods: Peripheral blood samples from 275 female breast cancer patients and 320 cancer free controls were used to detect three single nucleotide polymorphisms in IL-10 promoter region ( -1082, -819, -592 ) by PCR method. Results: The frequency of genotypes and alleles of three mentioned regions of IL-10 promoter and their haplotypes (GCC, ATA, and ACC) showed no statistically significant difference between patients and controls. In the case of prognostic factors, progesterone receptor (PR) status exhibited significant relation with -1082 genotypes (P=0.03) and haplotypes (P=0.02). -1082 AA genotype was associated with negative PR expression whereas AG and GG genotypes of this site were positively associated with PR expression. Similarly GCC haplotype correlated with positive PR expression and ATA and ACC with negative PR expression. Conclusion: The data of this study showed that IL-10 promoter gene polymorphisms may not be considered as one of the risk factors for breast cancer in Iranian patients.
Dawar Amani; Zohair Mohammad Hassan; Fatemeh Ravangard; Susan Frazmand; Mojtaba Karim Zadeh
Volume 2, Issue 2 , June 2005, , Pages 117-122
Abstract
Background: Invasive ductal carcinoma is the most common type of breast cancer in Iran. Impaired immune responses occur frequently in cancer patients, but the mechanisms of the induced immune defects remain poorly understood. It is believed that infiltrated immune cells, especially macrophages, may provide ...
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Background: Invasive ductal carcinoma is the most common type of breast cancer in Iran. Impaired immune responses occur frequently in cancer patients, but the mechanisms of the induced immune defects remain poorly understood. It is believed that infiltrated immune cells, especially macrophages, may provide help for tumor cell growth and metastasis. Objective: To analyze the status of tumor associated macrophages (TAM) by immunophenotyping method. Methods: Twenty-three women suffering from breast cancer were examined; nineteen of them were confirmed histologically to have invasive ductal carcinoma. Tumor cell suspensions from biopsy specimens and peripheral blood mononuclear cells from patients and matched controls were processed for analysis by flow cytometry. Results: No significant changes in the percentages of intra-tumor leukocytes and macrophages in the different stages of tumor were observed. There were no significant differences in the percentages of leukocytes (CD45 +), monocytes (CD45 +/CD14+) and activated monocytes (CD14+/HLA-DR+ and CD14+/CD16+) in the peripheral blood of patients and controls. Conclusion: The results of this study indicated that human breast cancer contain substantial, although variable numbers of macrophages, however, the activation status of these macrophages remain to be elucidated.