Publications by authors named "Abbas Ghaderi"

208 Publications

PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC.

Breast Dis 2021 Jan 25. Epub 2021 Jan 25.

Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity.

Objectives: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC).

Methods: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method.

Results: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients.

Conclusion: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.
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http://dx.doi.org/10.3233/BD-201049DOI Listing
January 2021

Investigation of TNF-α and IL-6 Levels in the Sera of Non-Melanoma Skin Cancer Patients.

Iran Biomed J 2021 03 1;25(2):88-92. Epub 2021 Sep 1.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: TNF-α and IL-6 are both pleiotropic cytokines playing major roles in cancer-associated cytokine networks. They have previously been investigated for their function in skin malignancies, mostly melanomas, and studies on non-melanoma skin cancer (NMSC) patients are relatively rara. In this study, we aimed to investigate the associations of serum levels of IL-6 and TNF-α with NMSCs and its clinicopathological features.

Methods: This cases-control study was carried out to assess the serum levels of TNF-α and IL-6 in 70 NMSC patients, in comparison with 30 healthy individuals, by means of flow cytometric bead-based immuneoassay.

Results: Serum levels of both TNF-α and IL-6 were significantly higher in NMSC patients (6.470 vs. 4.355 pg/ml; p = 0.0468, respectively), compared to healthy individuals (3.205 vs. 0.000 pg/ml; p = 0.0126, respectively). In the subgroup analysis, squamous cell carcinomas patients had higher serum levels of IL-6 compared to healthy individuals (3.445 vs. 0.000 pg/ml; p = 0.0432). No other significant differences were observed in the serum levels of these two cytokines among different clinicopathological subgroups of the patients.

Conclusion: The increased levels of TNF-α and IL-6 in NMSC patients can be introduced as an epiphenomenon of a complex cancer-induced cytokine cascade.
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http://dx.doi.org/10.29252/ibj.25.2.88DOI Listing
March 2021

Diversity of KIRs in invasive breast cancer patients and healthy controls along with the clinical significance in ER/PR/HER2+ patients.

Genes Immun 2020 12 30;21(6-8):380-389. Epub 2020 Nov 30.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Killer cell immunoglobulin-like receptors (KIR) consists of activating and inhibitory genes are essential for natural killer cell education. To determine the association of KIRs with susceptibility to invasive Breast cancer (BC), genotyping of 16 KIRs was performed by sequence-specific primers-polymerase chain reaction in 226 confirmed cases of BC with defined estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status and 226 healthy controls (CNs). We observed a lower frequency of 2DL1 and 2DS4del along with increased frequency of 2DS4fl in cases compared to CNs. Further analysis revealed a higher frequency of KIR2DL2, 2DS1, 2DS2,3DS1 in ER+ cases, 2DL2, 2DL5 in PR+ and 2DL1 in HER2+ cases compared to CNs. The detrimental role of KIR2DS4fl was observed in ER+ and PR+ cases whereas 2DS4del confers protection against ER+, PR+, and HER2+ cases. We noted the predisposing role of Bx genotype, KIR2DS1, 2DS2, 2DS5, 2DL2, 2DL5 for lymphatic invasion in ER+ cases along with a higher rate of lymph node metastasis (LNM) in carriers of Bx genotype and KIR2DS1 in ER+ cases. We suggest a link between B haplotype associated genes with the increased risk of lymphatic invasion and LNM, particularly in ER+ cases of BC.
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http://dx.doi.org/10.1038/s41435-020-00117-1DOI Listing
December 2020

Expression of TNFRs by B and T Lymphocytes in Tumor-Draining Lymph Nodes.

Methods Mol Biol 2021 ;2248:259-269

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Tumor necrosis factor alpha (TNF-α) has crucial roles in the induction or inhibition of various biological activities in immune and nonimmune cells. This cytokine mainly exerts its effects via two receptors named TNFR1 (CD120a) and TNFR2 (CD120b). Both B and T cells express TNFRs; however, opposing roles have been reported for TNF-α in the adaptive immunity. Lymph nodes (LNs), as the secondary lymphoid organs,  are one of the major places for the formation of immune responses against cancer. In this chapter, we explain the procedure as to how to isolate mononuclear cells from tumor-draining lymph nodes. In addition, we describe the process of surface staining with fluorochrome-conjugated antibodies for the assessment of the TNFRs expression by CD3, CD3CD4, CD3CD8, and CD19 lymphocytes by flow cytometry.
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http://dx.doi.org/10.1007/978-1-0716-1130-2_20DOI Listing
January 2021

Establishment of a bladder cancer cell line expressing both mesenchymal and epithelial lineage-associated markers.

Hum Cell 2021 Mar 9;34(2):675-687. Epub 2020 Nov 9.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Several experimental models including patient biopsies, animal models, and cell lines have been recommended to study the mechanism of bladder cancer development. After several passages in culture, cell lines lose some original features, and no longer resemble the cells of their original tumor. This makes it necessary to establish various cell lines. In an attempt to establish a new cell line for bladder cancer, JAM-ICR (RRID: CVCL_A9QB) was derived from a 64-year-old man diagnosed with a high-grade tumor. This cell line was characterized in multiple experiments involving morphological studies, immunophenotyping (by immunohistochemistry and flow cytometry), karyotyping, short tandem repeat analysis, colony-forming assays, migration and invasion assays, and chemosensitivity to anti-cancer drugs. JAM-ICR cells are pale with an irregular polygonal shape, and show some similarities to mesenchymal stem cells but with a wider shape and shorter arms. Phenotypic assessment demonstrated the simultaneous expression of mesenchymal-(vimentin, desmin, CD29, CD90, and CD106) and epithelial lineage (pan-cytokeratin) markers, which supports a phenotype similar to epithelial-mesenchymal transition for this cell line. JAM-ICR displayed high metastatic potential and stem-like properties, i.e., self-renewal, colony forming, and the coexpression of TRA-1 with CD44 and CD166. Furthermore, this cell line was significantly more resistant to doxorubicin in comparison to the 5637 cell line. These features make JAM-ICR a new bladder cancer cell line with metastatic potential and stem-like properties, which may be potentially useful as a model to elucidate the molecular and cellular mechanisms of bladder cancer pathogenesis or evaluate new drugs.
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http://dx.doi.org/10.1007/s13577-020-00456-1DOI Listing
March 2021

IL-27, a pleiotropic cytokine for fine-tuning the immune response in cancer.

Int Rev Immunol 2020 Nov 4:1-11. Epub 2020 Nov 4.

Shiraz Institute for Cancer Research, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Interleukin (IL)-27, a member of the IL-6/IL-12 family, has an important role in modulating inflammation in partnership with innate and adaptive immune cells. IL-27 binding to IL-27R starts downstream signaling based on the target cells. It can instigate inflammation by inducing CD4 T cell proliferation, Th1 polarization, cytotoxic T cell activation, generation of the natural killer cell, and macrophage and dendritic cell activation. However, by inducing programmed cell death and suppression of effector cells, IL-27 can suppress inflammation and return the immune response to hemostasis. Altogether, IL-27 displays multifaceted dual functions, which may result in either pro- or anti-inflammatory effects. Recent investigations indicated the antitumor activity of IL-27 via inducing Th1, and CTL responses and generating NK cells. On the other hand, IL-27 also can promote tumor cells' proliferation, survival, and angiogenesis. In the present review, we'll discuss recent advances concerning the role of IL-27 in inflammatory diseases such as infections, autoimmune diseases with a focus on cancer.
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http://dx.doi.org/10.1080/08830185.2020.1840565DOI Listing
November 2020

Regenerative effect of mesenteric fat stem cells on ccl4-induced liver cirrhosis, an experimental study.

Ann Med Surg (Lond) 2020 Dec 24;60:135-139. Epub 2020 Oct 24.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.

Methods: Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.

Results: After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.

Conclusion: Liver cirrhosis was induced. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status of the rats, as cirrhotic livers were regenerated back into normal appearing parenchyma. Rats' clinical behavior also reached healthy status.
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http://dx.doi.org/10.1016/j.amsu.2020.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593263PMC
December 2020

Significance of TIM-3 expression by CD4 and CD8 T lymphocytes in tumor-draining lymph nodes from patients with breast cancer.

Mol Immunol 2020 12 15;128:47-54. Epub 2020 Oct 15.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which is expressed by immune and nonimmune cells, has been shown to play immunoregulatory roles in the tumor microenvironment. In this study we assessed the expression of TIM-3 by T cells from tumor draining lymph nodes (TDLNs) of patients with breast cancer and its association with disease progression. Lymphocytes were isolated from 41 TDLNs, and flow cytometry was used to determine the expression of TIM-3 on CD4 and CD8 T cells, along with the simultaneous expression of CD25, Foxp3 and TIM-3 in CD4 T cells. The results showed that the frequency of TIM-3CD8 T cells was associated with higher tumor grade, and the geometric mean fluorescence intensity (gMFI) of TIM-3 in CD4 and CD8 T cells was significantly higher in patients with more than 9 involved lymph nodes than those with fewer involved nodes. The gMFI of TIM3 in CD4 T cells also showed a direct correlation with the number of metastatic lymph nodes. Phenotypic characterization of TIM-3CD4 T cells showed that the majority of CD4TIM3 lymphocytes were Foxp3 CD25 , and the majority of Foxp3CD25 regulatory T cells were TIM-3. Our findings showed that TIM-3 was expressed by CD4, CD8 and regulatory T cells in breast TDLNs, and that expression on CD4 and CD8 T cells was mostly associated with poor prognosticators such as a higher number of involved lymph nodes or higher tumor grade. More studies are required to confirm TIM-3 as a prognostic marker and a target for immunotherapy in breast cancer.
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http://dx.doi.org/10.1016/j.molimm.2020.10.002DOI Listing
December 2020

Low-Power Voltage Transformer Smart Frequency Modeling and Output Prediction up to 2.5 kHz, Using Sinc-Response Approach.

Sensors (Basel) 2020 Aug 29;20(17). Epub 2020 Aug 29.

Department of Electrical, Electronic and Information Engineering-Guglielmo Marconi, Alma Mater Studiorum-University of Bologna, Viale del Risorgimento 2, 40136 Bologna, Italy.

The instrument transformers scenario is moving towards the adoption of a new generation of low-power instrument transformers. This disruptive change also requires that the modeling, characterization, and testing of those devices must be improved. Therefore, this study focuses on a smart approach developed by the authors in a previous study to estimate the output of low-power voltage transformers (LPVT). The approach-which is based on a sort of modeling in the frequency domain (the so-called sinc-response)-allows obtaining the behavior of the LPVT at rated and distorted conditions. Experimental tests performed on off-the-shelf devices confirm the applicability and effectiveness of the proposed approach when estimating the output response of LPVTs.
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http://dx.doi.org/10.3390/s20174889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506876PMC
August 2020

CD4CD25FoxP3 T cells: a distinct subset or a heterogeneous population?

Int Rev Immunol 2020 Jul 24:1-10. Epub 2020 Jul 24.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

In addition to generating effective immunity against infectious agents, the immune system helps to fight against different noninfectious human diseases while maintaining the balance between self and non-self discrimination. The breakdown of tolerance in autoimmune diseases or sustainable tolerance in an abnormal microenvironment such as chronic inflammation may initiate the process of malignancy. Immune system regulation is controlled by a complex, dynamic network of cells and mediators. Understanding the cellular and molecular basis of immune regulation provides better insight into the mechanisms governing the immune pathology of diseases. Among several cellular subsets and mediators with regulatory roles, a subpopulation of CD4 T cells was recently reported to be positive for FoxP3 and negative for CD25, with a suggested range of functional activities in both cancer and autoimmune diseases. This CD4 subset was first reported in 2006 and thought to have a role in the pathogenesis of cancer. However, the spectrum of roles played by this T cell subset is broad, and no consensus has been reached regarding its immunological functions. In this review, we focused on the possible origin of CD4CD25FoxP3 T cells and their function in cancer and autoimmune diseases.
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http://dx.doi.org/10.1080/08830185.2020.1797005DOI Listing
July 2020

The balance of regulatory and stimulatory B cell subsets in breast cancer draining lymph nodes correlates with tumor prognostic factors.

Life Sci 2020 Sep 18;257:118117. Epub 2020 Jul 18.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Aims: B cells can promote or inhibit immune responses against breast cancer. We investigated changes in the frequency of B cells with stimulatory or regulatory capacity in breast tumor draining lymph nodes during cancer progression.

Main Methods: We isolated mononuclear cells from fresh axillary lymph nodes (LNs) of 44 patients with breast cancer and stained lymphocytes with antibodies against CD19, CD80, CD86, CD39 and CD73. To assess programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) expression, lymphocytes were briefly stimulated, stained for CD19, PD-1 and PD-L1, and examined with flow cytometry.

Key Findings: The frequency of CD80 B cells was higher in nonmetastatic lymph nodes, while the percentage of CD86 B cells showed a positive relationship with higher tumor grade and higher numbers of involved LNs. A small proportion of unstimulated B cells expressed PD-1 or PD-L1 but these molecules were rapidly upregulated on B cells following activation. The frequency of stimulated PD-L1 B cells showed an inverse association with estrogen and progesterone receptor expression and a nonsignificant positive association with tumor grade. In addition, the percentage of unstimulated PD-1 B cells was higher in patients with higher-grade tumors. CD73 expression on B cells was associated with lower numbers of involved LNs, and the frequency of CD39 B cells was higher in patients with larger tumors.

Significance: CD86, CD39, PD-1 and PD-L1 B cells showed associations with poor prognostic factors, therefore their potential role in the suppression of the immune responses against breast cancer should be evaluated in greater detail.
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http://dx.doi.org/10.1016/j.lfs.2020.118117DOI Listing
September 2020

Clinical relevance and prognostic significance of PD-1/PD-Ls in non-metastatic bladder cancer: A role for PD-L2.

Mol Immunol 2020 08 5;124:35-41. Epub 2020 Jun 5.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: Bladder cancer (BC) can be successfully treated by manipulating immune responses with intravesical Bacillus Calmette-Guerin instillation or targeting the PD-1/PD-L signaling pathway. In the present study we investigated the prognostic significance of the immune checkpoint inhibitor PD-1 and its ligands PD-L1 and PD-L2 on tumor cells and infiltrating lymphocytes, in the tumor microenvironment and draining lymph nodes in patients with non-metastatic BC.

Patients And Methods: Cells were mechanically isolated from tissues and draining lymph nodes from 58 patients, and surface-stained for CD45, PD-1, PD-L1 and PD-L2. The cells were then analyzed with a flow cytometric method.

Results: Approximately 2% of CD45-negative tumor and stromal cells expressed PD-L1. Expression was not associated with the main clinicopathological characteristics of the disease or with survival. However, as tumors progressed the frequency of PD-L1CD45 cells and the mean expression of PD-1 on CD45 cells increased remarkably on immune cells in tumor tissues and draining lymph nodes. In addition, frequency analysis showed that cell percentages as well as mean expression of PD-L2 on total CD45 lymphocytes and their CD45 subpopulation in tumor-draining lymph nodes was significantly associated with cancer-related death (P < 0.05). Multiple Cox regression also revealed that while CD45 (hazard ratio: 0.596, 95 % CI 0.439-0.809, P = 0.001) was associated with improved survival, CD45 (HR: 0.615, 95 % CI 0.454-0.831, P = 0.002), and PD-L2CD45 cells (hazard ratio: 1.472, 95 % CI 1.023-2.120, P = 0.038) in draining lymph nodes were associated with lower survival.

Conclusion: Our results suggest that in patients with BC, PD-1 and PD-L expression on immune cells, especially in draining lymph nodes, is valuable for predicting prognosis and survival, and possibly responsiveness to immunotherapy. However, expression of the inhibitor molecule or its ligands on tumor cells was not associated with prognosis. The results highlight the significance of PD-L2 as a second important suppressive molecule in tumors.
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http://dx.doi.org/10.1016/j.molimm.2020.05.010DOI Listing
August 2020

The Significance of Biobanking in the Sustainability of Biomedical Research: A Review.

Iran Biomed J 2020 07 12;24(4):206-13. Epub 2020 Feb 12.

Shiraz Institute for Cancer Research, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Biobank, defined as a functional unit for facilitating and improving research by storing biospecimen and their accompanying data, is a key resource for advancement in life science. The history of biobanking goes back to the time of archiving pathology samples. Nowadays, biobanks have considerably improved and are classified into two categories: diseased-oriented and population-based biobanks. UK biobank as a population-based biobank with about half a million samples, Biobank Graz as one of the largest biobanks in terms of sample size, and The International Agency for Research on Cancer biobank as a specialized the World Health Organization cancer agency are few examples of successful biobanks worldwide. The present review provides a history of biobanking, and after presenting different biobanks, we discuss in detail the challenges in the field of biobanking and its future, as well. In the end, ICR biobank, as the first cancer biobank in Iran established in 1998, is thoroughly described.
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http://dx.doi.org/10.29252/ibj.24.4.206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275812PMC
July 2020

KIR Variation in Iranians Combines High Haplotype and Allotype Diversity With an Abundance of Functional Inhibitory Receptors.

Front Immunol 2020 2;11:556. Epub 2020 Apr 2.

Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, United States.

Natural killer (NK) cells are innate lymphocytes that eliminate infected and transformed cells. They discriminate healthy from diseased tissue through killer cell Ig-like receptor (KIR) recognition of HLA class I ligands. Directly impacting NK cell function, polymorphism associates with infection control and multiple autoimmune and pregnancy syndromes. Here we analyze diversity of 241 individuals from five groups of Iranians. These five populations represent Baloch, Kurd, and Lur, together comprising 15% of the ethnically diverse Iranian population. We identified 159 alleles, including 11 not previously characterized. We also identified 170 centromeric and 94 telomeric haplotypes, and 15 different haplotypes carrying either a deletion or duplication encompassing one or more complete genes. As expected, comparing our data with those representing major worldwide populations revealed the greatest similarity between Iranians and Europeans. Despite this similarity we observed higher frequencies of in Iran than any other population, and the highest frequency of HLA-B51, a Bw4-containing allotype that acts as a strong educator of NK cells. Compared to Europeans, the Iranians we studied also have a reduced frequency of , which encodes an allotype that is not expressed at the NK cell surface. Concurrent with the resulting high frequency of strong viable interactions between inhibitory KIR and polymorphic HLA class I, the majority of haplotypes characterized do not express a functional activating receptor. By contrast, the most frequent haplotype in Iran expresses only one functional inhibitory KIR and the maximum number of activating KIR. This first complete, high-resolution, characterization of the locus of Iranians will form a valuable reference for future clinical and population studies.
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http://dx.doi.org/10.3389/fimmu.2020.00556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142237PMC
April 2020

CD8-positive memory T cells in tumor-draining lymph nodes of patients with breast cancer.

BMC Cancer 2020 Mar 30;20(1):257. Epub 2020 Mar 30.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-1798, Shiraz, Iran.

Background: Human immunological memory is a hallmark of the adaptive immune system and plays an important role in the development of effective immune responses against tumors. In the present study, we aimed to determine the frequencies of CD8 memory T cell subsets including T stem cell memory (TSCM) in tumor-draining lymph nodes of patients with breast cancer (BC).

Methods: Mononuclear cells were obtained from axillary lymph nodes of 52 untreated patients with BC and stained for CD8, CCR7, CD45RO, CD95 markers to detect different subtypes of memory cells in the CD8 lymphocyte population. Data were acquired on four-color flow cytometer and analyzed with CellQuest Pro software.

Results: We observed that 47.65 ± 2.66% of CD8 lymphocytes expressed the CD45RO, a marker for memory T cells. Statistical analysis showed that the total frequency of central memory T cells (TCM) and their subset with low CD45RO expression was significantly higher in tumor-involved nodes compared to tumor-free ones (P = 0.024 and P = 0.017, respectively). The level of CD95 expression (based on mean fluorescence intensity) on the surface of TCM, their CD45RO and CD45RO subsets, and TSCM was higher in patients with stage II compared to those in stage I (P < 0.05). In addition, the percentage of naive CD8 T cells was significantly lower in tumor-involved lymph nodes compared to tumor-free ones (P = 0.025).

Conclusions: Our data collectively indicate no significant differences in the frequencies of CD8 lymphocytes or their memory subsets in tumor-draining lymph nodes of patients with BC. However, the frequency of CD45 TCM was higher in tumor-involved nodes. Along with a decrease in the frequency of naive T cells, the higher frequency of CD45 TCM suggests that despite the immune reaction to provide a pool of effective memory cells, it is blocked in early-stage of memory cells' differentiation (CD45RO), probably by tumor-derived suppressive factors. Identifying the molecular and cellular mechanisms behind this suppression can provide invaluable tools for adoptive T cell therapies in cancer.
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http://dx.doi.org/10.1186/s12885-020-6714-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106627PMC
March 2020

Biobank; An Essential Infrastructure for the Future of Personalized Medicine.

Arch Iran Med 2020 01 1;23(1):59-60. Epub 2020 Jan 1.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

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January 2020

Positive association of Bx genotype, KIR2L5, KIR2DS5 and full-length KIR2DS4 with the risk of meningioma.

Immunobiology 2020 03 19;225(2):151900. Epub 2019 Dec 19.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: NK cells as a part of innate immune system, are controlled by a set of activating and inhibitory KIR receptors (aKIR, iKIR) which are implicated in tumor microenvironment immunity through a variety of activating and inhibitory immune signals. KIRs are multi gene family receptors that differ in the number and type of genes among individuals. In the current research we determined the KIRs genes and genotypes impact on predisposition to meningioma development in Iranians.

Methods: Sequence-specific primers-polymerase chain reaction (SSP-PCR) was performed for genotyping of 16 KIRs in 159 meningioma cases and 362 age and sex matched healthy controls (CNs) at Shiraz Institute for Cancer Research.

Results: Comparison of the KIR genotypes frequencies between cases and controls disclosed a highly significant increase in Bx genotype, CxTx subset and Cen AB and Tel AB in meningioma cases and a decrease in AA genotype, C4Tx subset and Cen AA, Tel AA, Tel BB in healthy controls. Among all 16 KIR genes, the carriers of KIR2DL5 and KIR2DS5 constituted a much greater proportion in meningioma than control group. Comparison of carrier frequencies of KIR2DS4 variants between case and controls revealed a higher frequency of KIR2DS4 full length (KIR2DS4fl) in meningioma cases and a lower frequency of KIR2DS4 deleted variant (KIR2DS4del) in controls. Furthermore, the simultaneous presence of 2DS5, 2DS4fl, CenAB, TelAB and absence of 2DS4del, CenAA, TelAA, TelBB, magnify the risk of developing meningioma substantially (OR ≈ 23). Altogether, 41 distinct KIR genotypes were characterized in 521 subjects. Among them, some individuals were characterized by seven peculiar genotypes that the linkage disequilibrium between KIR2DS2-KIR2DL2 and KIR2DL5-KIR2DS3-KIR2DS5 has not been detected. The carriers of certain genotypes with presence of as KIR2DL5 and absence of KIR2DS3, KIR2DS5 constituted a much higher proportion in meningioma than control group which increase the risk of meningioma up to 72 times.

Conclusion: This case- control study suggests carriers of Bx genotype, KIR2DL5, KIR2DS5, 2DS4fl, ≥ 4 iKIR, CxTx subset as well as Cen AB and Tel AB are associated with an increased risk of developing meningioma whereas carrying KIR2DS4del, AA, C4TX genotypes and Cen AA, Tel AA, Tel BB reduce the genetic predisposition for meningioma.
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http://dx.doi.org/10.1016/j.imbio.2019.151900DOI Listing
March 2020

Effects of Thermal Cycles on Interfacial Pressure in MV Cable Joints.

Sensors (Basel) 2019 Dec 27;20(1). Epub 2019 Dec 27.

Department of Electrical, Electronic and Information Engineering, Guglielmo Marconi Alma Mater Studiorum, University of Bologna, Viale del Risorgimento 2, 40136 Bologna, Italy.

The use of medium voltage cable joints is mandatory when dealing with power cable faults and the installation of new lines. However, such an accessory is among the top causes of faults among the grid. To this purpose, one of the quantities monitored to understand the causes of such faults is the interfacial pressure between the insulating layers of the cable joint. In this work, the interfacial pressure between Cross-linked polyethylene (XLPE) and silicon rubber has been evaluated when the cable joint experiences thermal cycles. From the results, the pressure variation caused by the thermal cycles is demonstrated. Such a phenomenon may be connected to the generation of voids and weak spots that accelerate cable joint ageing. Therefore, proper comments and conclusions are drawn.
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http://dx.doi.org/10.3390/s20010169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983006PMC
December 2019

Significance of TC9 and TH9 in Helicobacter pylori-induced gastritis.

Helicobacter 2020 Feb 5;25(1):e12672. Epub 2019 Dec 5.

Clinical Microbiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: H pylori plays a critical role in the development of stomach cancer, especially in people affected by the bacteria at an early stage of life. Th9 cells and IL-9 play major roles in immune responses against various infections. IL-9 is influential in chronic or acute inflammation of the mucosa.

Aim: This study seeks to investigate the possible functions of Tc9, Th9 cells, and IL-9 level in patients with inflammation due to H pylori infection.

Methods: Eighty-three patients with dyspepsia symptoms and twenty normal subjects with no sign and symptoms of dyspepsia were recruited. Frequencies of T-cell subsets were determined by flow cytometry. Levels of cytokines IL-9 family in the sera and supernatants of antigen-activated PBMCs patients were measured by ELISA and flow cytometry.

Results: The participants included 56 females and 47 males with a mean age of 39.2 ± 15.3 years. We assigned the infected group into peptic ulcer and gastritis (chronic active and chronic). Frequencies of Tc9, Th17, Tc17, Th17/9, and Tc17/9 increased significantly in the peptic ulcer, chronic active, and chronic gastritis, compared with the uninfected and healthy control groups. A significant increase was seen in IL-9, IL-4, and IL-23 in the chronic active gastritis. Further observed was a significant increase in IL-21 and a decrease in IL-10 in the infected groups.

Conclusion: The results revealed that increased Tc9, Th17/9, and Tc17/9 cells appear to be influential in the progression and severity of H pylori infection. Also, increased IL-9 and IL-4 levels and Tc9, Tc17/9, and Th17/9 were seen in chronic active gastritis patients. These findings may provide useful information for a therapeutic targeting of chronic active H pylori infections.
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http://dx.doi.org/10.1111/hel.12672DOI Listing
February 2020

KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.

Exp Mol Pathol 2020 02 18;112:104345. Epub 2019 Nov 18.

Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Iran. Electronic address:

Backgrounds: Our previous study has suggested that KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with head and neck squamous cell carcinoma (HNSCC) development. The purpose of the current study was to investigate the possible association of killer cell immunoglobulin like receptors (KIRs) gene with the clinicopathological features of patients.

Methods: We reviewed the pathological reports of 285 pathologically confirmed cases of HNSCC and analyzed the association of KIR system with pathological characteristics.

Results: A significant increase was demonstrated in the carrier frequency of KIR2DS4 in conventional than basaloid type and a higher frequency of lymph node metastasis (LNM) in carriers of KIR2DL2 and individuals possess 5 inhibitory KIRs (iKIRs). We also observed a higher proportion of patients with advanced stage of HNSCC in carriers of KIR2DL2 and deleted variant of KIR2DS4.

Conclusion: In HNSCC, KIR2DL2 is positively while KIR2DS4 is negatively associated with advanced stage. The higher proportion of LNM in carriers of KIR2DL2 and carriers of 5 iKIRs, suggested that inhibitory KIRs are associated with metastatic risk.
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http://dx.doi.org/10.1016/j.yexmp.2019.104345DOI Listing
February 2020

Helios, CD73 and CD39 Induction in Regulatory T Cells Exposed to Adipose Derived Mesenchymal Stem Cells.

Cell J 2020 Jul 14;22(2):236-244. Epub 2019 Oct 14.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic

Objective: Mesenchymal stem cells (MSCs) have prominent immunomodulatory roles in the tumor microenvironment. The current study intended to elucidate Treg subsets and their cytokines after exposing naïve T lymphocytes to adiposederived MSCs (ASCs).

Materials And Methods: In this experimental study, to obtain ASCs, breast adipose tissues of a breast cancer patient and a normal individual were used. Magnetic cell sorting (MACS) was employed for purifying naïve CD4 T cells from peripheral blood of five healthy donors. Naïve CD4 T cells were then co-cultured with ASCs for five days. The phenotype of regulatory T cells (Tregs) and production of interleukine-10 (IL-10), transforming growth factor beta (TGF-β) and IL-17 were assessed using flow cytometry and ELISPOT assays, respectively.

Result: CD4CD25FOXP3CD45RA Tregs were expanded in the presence of cancer ASCs but CD4CD25Foxp3CD45RA regulatory T cells were up-regulated in the presence of both cancer- and normal-ASCs. This up-regulation was statistically significant in breast cancer-ASCs compared to the cells cultured without ASCs (P=0.002). CD4CD25 FOXP3Helios, CD4CD25 FOXP3Helios and CD25 FOXP3CD73CD39 Tregs were expanded after co-culturing of T cells with both cancer-ASCs and normal-ASCs, while they were statistically significant only in the presence of cancer-ASCs (P<0.05). Production of IL-10, IL-17 and TGF-β by T cells was increased in the presence of either normal- or cancer-ASCs; however, significant effect was only observed in the IL-10 and TGF-β of cancer-ASCs (P<0.05).

Conclusion: The results further confirm the immunosuppressive impacts of ASCs on T lymphocytes and direct them to specific regulatory phenotypes which may support immune evasion and tumor growth.
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http://dx.doi.org/10.22074/cellj.2020.6313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874788PMC
July 2020

Atypical Memory and Regulatory B Cell Subsets in Tumor Draining Lymph Nodes of Head and Neck Squamous Cell Carcinoma Correlate with Good Prognostic Factors.

Head Neck Pathol 2020 Sep 5;14(3):645-656. Epub 2019 Nov 5.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and function in tumor draining lymph nodes (TDLNs) is still incomplete. This study aimed to investigate changes in the phenotypic profile of B cells in TDLNs of head and neck squamous cell carcinoma (HNSCC) during disease progression. Mononuclear cells were isolated from TDLNs and stained with antibodies for CD19 and other B cell-related markers and analyzed by flow cytometry. CD19 B cells comprised 38.6 ± 8.9% of lymphocytes in TDLNs of HNSCC. Comparison of metastatic and non-metastatic LNs disclosed no significant differences in the frequencies of B cell subsets including antigen-experienced, naïve, switched, unswitched, atypical memory, marginal zone-like B cells, and B cells with regulatory phenotypes. The percentage of atypical memory (CD27IgMIgD) B cells was significantly higher in patients with tongue SCC with no involved LNs (p = 0.033) and correlated inversely with the number of involved LNs. The frequency of CD24CD38 B cells was significantly higher in non-metastatic LNs of patients with grade I compared to grade II (p = 0.016), and the percentage of CD5 B cells decreased as tumors progressed from stage III to IV (p = 0.008). Our data show that in TDLNs of HNSCC, the frequency of B cells with atypical memory and regulatory phenotypes was significantly associated with good prognostic factors; however, their function remains to be investigated.
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http://dx.doi.org/10.1007/s12105-019-01095-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413970PMC
September 2020

Cytokine profile of CD4CD25FoxP3 T cells in tumor-draining lymph nodes from patients with breast cancer.

Mol Immunol 2019 12 17;116:90-97. Epub 2019 Oct 17.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: A T cell subtype with the CD4CD25FoxP3 phenotype was recently described. We aimed to investigate the frequency of these cells and their ability to produce cytokines in tumor-draining lymph nodes from patients with breast cancer (BC).

Materials And Methods: Mononuclear cells from lymph nodes of 20 patients with BC were activated and stained for appropriate markers. The cells were assayed with four-color flow cytometry.

Results: A very small fraction of CD4CD25FoxP3 cells produced cytokines at levels that were significantly lower than in the regulatory (CD4CD25FoxP3) and effector cell (CD4CD25FoxP3) subpopulations. The expression of IFNγ and IL-2 in the CD4CD25FoxP3 subset was significantly higher than in Treg cells, but lower than in the effector subset. Conversely, IL-22 expression in Treg cells was significantly higher than in the CD4CD25FoxP3 subpopulation. The expression of IL-10 in the CD4CD25FoxP3 subset was also significantly higher than in effector cells.

Conclusion: We suggest that CD4CD25FoxP3 cells in patients with BC are exhausted cells with an intermediate phenotype between effector and regulatory cells.
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http://dx.doi.org/10.1016/j.molimm.2019.10.007DOI Listing
December 2019

Uncertainty Analysis of a Test Bed for Calibrating Voltage Transformers vs. Temperature.

Sensors (Basel) 2019 Oct 15;19(20). Epub 2019 Oct 15.

This paper is an extended version of our paper published in: Mingotti, A..

The paper addresses the evaluation of the uncertainty sources of a test bed system for calibrating voltage transformers vs. temperature. In particular, the Monte Carlo method has been applied in order to evaluate the effects of the uncertainty sources in two different conditions: by using the nominal accuracy specifications of the elements which compose the setup, or by exploiting the results of their metrological characterization. In addition, the influence of random effects on the system accuracy has been quantified and evaluated. From the results, it emerges that the choice of the uncertainty evaluation method affects the overall study. As a matter of fact, the use of a metrological characterization or of accuracy specifications provided by the manufacturers provides respectively an accuracy of 0.1 and 0.5 for the overall measurement setup.
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http://dx.doi.org/10.3390/s19204472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832277PMC
October 2019

Expression of major histocompatibility complex class I polypeptide-related sequence B in adipose-derived stem cells from breast cancer patients and normal individuals.

J Cancer Res Ther 2019 Jul-Sep;15(5):1067-1072

Shiraz Institute for Cancer Research, School of Medicine; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Context: Through the expression of different immunomodulatory molecules, mesenchymal stem cells (MSCs) play a significant role in the regulation of immune responses against tumor cells. Herein, the expression of major histocompatibility complex class I polypeptide-related sequence B (MIC B) as an immunomodulatory molecule was investigated on adipose-derived stem cells (ASCs) isolated from breast cancer patients (Stage II and III) and healthy individuals.

Materials And Methods: ASCs were isolated enzymatically, and the expression of MIC B was measured using quantitative real-time polymerase chain reaction method before and after treatment with interferon γ (IFN-γ). The concentration of MIC B in the supernatant of ASCs and also sera of breast cancer and normal individuals were determined using ELISA method.

Results: The expression of MIC B in normal ASCs and Stage II ASCs was higher than Stage III ASCs. However, after treatment with IFN-γ expression of MIC B in ASCs was conversely changed as cancer ASCs showed approximately 3.5 fold higher expression of MIC B compared to normal ASCs. The mRNA expression of MIC B in Stage III, Stage II, and normal ASCs showed 61 (P = 0.02), 13 (P = 0.01) and 3 (P > 0.05) fold higher expression after stimulation with IFN-γ compared to cells with no stimulation.

Conclusion: Expression of MIC B and upregulation of this molecule in response to IFN-γ in cancer ASCs draw attention to the effective role of MSCs in the tumor microenvironment. However, more studies will be needed to further elucidate Natural-killer Group 2, member D (NKG2D) ligands-dependent immunomodulatory roles of ASCs in the tumor progression.
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http://dx.doi.org/10.4103/jcrt.JCRT_866_16DOI Listing
July 2020

Molecular Cloning, Expression and Purification of G-CSF Isoform D, an Alternative Splice Variant of Human G-CSF.

Iran J Allergy Asthma Immunol 2019 Aug 17;18(4):419-426. Epub 2019 Aug 17.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Granulocyte colony-stimulating factor (G-CSF) is the major regulator of hemopoiesis and granulopoiesis. However, overexpression of G-CSF has been implicated in several important processes in tumor biology such as tumor growth, angiogenesis, and metastasis. Four different mRNA isoforms resulting from alternative splicing have been reported for G-CSF (transcript variants 1, 2, 3 and 4). The mRNAs and protein products of splice variants 1 and 2 have been isolated for the first time, from tumor cell lines. In the present study for the first time we isolated the G-CSF transcript variant 4 encoding G-CSF isoform D from a highly malignant tumor cell line (Mehr80) with overexpression of G-CSF. Both the full-length G-CSF isoform B and G-CSF isoform D were cloned from Mehr80 cell line, overexpressed in Escherichia coli as N-terminal glutathione-S-transferase fusion proteins in the form of inclusion bodies and affinity purified by the batch method using glutathione-Sepharose 4B resin. Both fusion proteins were successfully cloned and expressed. Folded recombinant proteins were solubilized from inclusion bodies using sarkosyl, Triton X-114 and CHAPS and purified. The purity of G-CSF isoforms was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and they were clearly detected in western blot analysis using anti-G-CSF polyclonal antibody. The G-CSF plays various roles in physiological and pathological conditions, however to date, the differential function of G-CSF isoforms remains unknown. Considering the fact that G-CSF isoform D was isolated from a highly malignant tumor cell line with overexpression of G-CSF, the role of this splice variant in tumorigenesis requires further investigation.
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http://dx.doi.org/10.18502/ijaai.v18i4.1420DOI Listing
August 2019

In vitro cytotoxic effect of Trastuzumab in combination with Pertuzumab in breast cancer cells is improved by interleukin-2 activated NK cells.

Mol Biol Rep 2019 Dec 6;46(6):6205-6213. Epub 2019 Sep 6.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Targeting erb-b2 receptor tyrosine kinase 2 (ERBB2) using the combination of Trastuzumab and Pertuzumab has demonstrated promising results in breast cancer therapy. It has further been revealed that interleukin-2 (IL-2) can activate Natural Killer cells (NK cells) and elevate their cytotoxic potency against tumor cells. In this study, we explored the cytotoxic effect of recombinant human IL-2 in combination with Trastuzumab and Pertuzumab on the ERBB2 positive (SK-BR-3) and negative (MDA-MB-231) breast cancer cell lines. The cytotoxicity level of IL-2 activated NK cells (approximately 75%) were significantly higher than untreated cells (approximately 55%) in the presence of Trastuzumab and Pertuzumab against SK-BR-3 cells, while no difference was observed in the case of MDA-MB-231 cells (about 15%).
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http://dx.doi.org/10.1007/s11033-019-05059-0DOI Listing
December 2019

Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.

Mol Immunol 2019 10 26;114:172-178. Epub 2019 Jul 26.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB B cells were perforin-negative. Both naïve (CD24CD27) and active/memory (CD24CD27) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB B cells in breast tumor immunity.
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http://dx.doi.org/10.1016/j.molimm.2019.07.019DOI Listing
October 2019

Probiotic potential comparison of Lactobacillus strains isolated from Iranian traditional food products and human feces with standard probiotic strains.

J Sci Food Agric 2019 Dec 17;99(15):6680-6688. Epub 2019 Sep 17.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Traditional fermented products are a rich source of microorganisms which may have remarkable probiotic properties even more significant than probiotic strains of human origin. In this study three Lactobacillus plantarum and one Lactobacillus fermentum strains, isolated from either Iranian traditionally fermented products or children's feces, identified with molecular methods and selected based on high acid resistance, were investigated for their probiotic properties in vitro and compared with standard probiotic strains of the species; L. plantarum ATCC 14917, L. fermentum PTCC 1744 and L. acidophilus ATCC 4356.

Results: Most of the isolates showed a high survival rate under gastrointestinal tract conditions and L. plantarum strains displayed a moderate ability to adhere to human colon adenocarcinoma cell line, HT-29. Neutralized cell free culture supernatants of L. plantarum strains were capable of inhibiting pathogens. Almost all of the strains were resistant to vancomycin and streptomycin and susceptible to other clinically relevant antibiotics. Isolated strains exhibited low to moderate autoaggregation (Auto-A), co-aggregation (Co-A) and hydrophobicity, following a strain specific manner. None of the strains invaded into HT-29 cells while strain PF11 could significantly decrease the number of adhering pathogenic bacteria. Most of the strains increased apoptosis of HT-29 cells, though they had no effect on human umbilical vein endothelial cells (HUVECs).

Conclusion: Favorable probiotic properties of strains PL4 and PF11 along with their anticancer activity imply their potential for clinical or technological applications. However, further in vitro/in vivo investigations are recommended. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.9945DOI Listing
December 2019

Activating and inhibitory killer cell immunoglobulin like receptors (KIR) genes are involved in an increased susceptibility to colorectal adenocarcinoma and protection against invasion and metastasis.

Immunobiology 2019 09 20;224(5):681-686. Epub 2019 Jun 20.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: A set of activating and inhibitory KIRs (aKIR, iKIR) are involved in NK cell mediated immunity. This study was carried out in order to investigate the KIRs pattern and its association with colorectal carcinoma (CRC) development and clinical outcomes.

Methods: Sequence-specific primers-polymerase chain reaction (SSP-PCR) for typing of 16 KIR genes was utilized in 165 patients with colorectal adenocarcinoma with 165 age and gender matched healthy controls (CNs).

Results: Possessing KIR2DS1, 2DS5, 3DS1, 2DS4fl, 2DL5, telomeric half KIR genes, ≥ 4 aKIR and CXT4 genotype were associated with an increased susceptibility to colorectal adenocarcinoma while KIR2DS4del and iKIR >aKIR confer resistance to CRC. On the other hand, clinical associations revealed the defensive role of telomeric KIR3DL1, 3DS1, 2DS1, 2DS4, genotypes with ≥ 4 aKIR and more inhibitory KIRs than activating ones (I > A) against metastasis and CXTX genotype in perineural invasion.

Conclusion: According to current results it appears that KIRs system play distinctive roles in development and metastasis of colorectal adenocarcinoma.
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http://dx.doi.org/10.1016/j.imbio.2019.06.002DOI Listing
September 2019