Publications by authors named "Shima Azadpour"

6 Publications

  • Page 1 of 1

Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies.

Blood 2020 04;135(15):1287-1298

CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.
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http://dx.doi.org/10.1182/blood.2019003186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146024PMC
April 2020

Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study.

Biol Blood Marrow Transplant 2020 03 19;26(3):438-444. Epub 2019 Nov 19.

Division of Pediatric Hematology/Oncology/Blood & Marrow Transplant, BC Children's Hospital, Vancouver, British Columbia, Canada; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address:

Anti-thymocyte globulin (ATG) is an established approach to decrease chronic GVHD (cGVHD), yet the exact mechanism is uncertain. To better understand the mechanism of action of ATG in preventing cGVHD, we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group (CBMTG) 0801 trial, which demonstrated a significant impact of ATG on cGVHD. In a separate companion biology study, we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients. Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21 B cells, CD56 NK cells, and T cells ST2, osteopontin, soluble B-cell activating factor (sBAFF), Interleukin-2 receptor alpha (sCD25), T-cell immunoglobulin and mucin domain-3 (TIM-3), matrix metallopeptidase 3, ICAM-1, C-X-C motif chemokine 10 (CXCL10), and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56 NK cells (P < .0001). T cells, conventional Th cells, CD21 B cells, and all plasma markers were not affected. In the populations most affected by ATG, changes in naive Th cells were associated with the later development of cGVHD. This analysis suggests that ATG primarily impacts on cGVHD through suppression of naive Th cell expansion after transplantation. These associations need to be validated in additional studies.
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http://dx.doi.org/10.1016/j.bbmt.2019.11.015DOI Listing
March 2020

KRAS mutation and abnormal expression of Cripto-1 as two potential candidate biomarkers for detection of colorectal cancer development.

J Cell Biochem 2020 04 6;121(4):2901-2908. Epub 2019 Nov 6.

Colorectal Cancer Research Center, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Colorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto-1 (CR-1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty-five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR-1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR-1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR-1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR-1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development.
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http://dx.doi.org/10.1002/jcb.29526DOI Listing
April 2020

Platelet storage media change the expression characteristics of the platelet-derived microparticles.

Indian J Hematol Blood Transfus 2014 Sep 24;30(3):169-74. Epub 2013 Jan 24.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, IBTO Bldg., Hemmat. Exp. Way, Next to the Milad Tower, P.O. Box 14665-1157, Tehran, Iran.

Activated platelets shed microparticles in vivo and definitely in vitro upon aging under storage. Studies about the platelet-derived microparticles (PMPs) produced in different storage media of PC were very limited. The aim of this research was to compare some surface molecules of these microvesicles in dissimilar microenvironments; plasma and the candidate medium for the platelet concentrate, Composol. Thirty units of PCs were prepared from Iranian Blood Transfusion Organization. Each unit was divided into two portions. In one of the portions, plasma was replaced with Composol using a connecting device instrument. MPs were isolated from PC and the levels of PS exposure (the annexin-binding capacity) and binding to vWF were surveyed on their surface using ELISA and flow cytometry techniques. The levels of PS exposure were increased on MPs during 7 days storage in the both media but the differences were not significant (P value >0.05). In addition, binding of PMP to vWF was declined during storage. The binding capabilities of PMP were significantly higher in Composol than that of plasma at the day 4 or 7 of storage (P value = 001). It seemed that the binding of PMPs to vWF was affected from the storage media of PC (plasma and Composol) but PS exposure was not affected from the type of storage media.
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http://dx.doi.org/10.1007/s12288-012-0227-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115080PMC
September 2014

Glycoproteins of GpIbα and GpIIbIIIa on the Synthetic or Naturally Occurred Platelet-Derived Microparticles.

Indian J Hematol Blood Transfus 2013 Sep 4;29(3):134-8. Epub 2012 Jul 4.

Iranian Blood Transfusion Organization Research Center, High Institute for Research and Education in Transfusion Medicine, P.O. Box 14665-1157, Tehran, Iran.

Infusible platelet membranes (IPM) prepared from new or outdated human platelets have been developed as an alternative to standard platelet concentrates (PCs), with the additional advantage of long shelf life and increased viral safety. Lack of gpIIb/IIIa has been reported as one of the properties of the IPM microparticles. In re-examining this issue, we studied the molecules of gpIIb/IIIa and gpIbα on the surface of IPM microparticles. These molecules could better evaluate the functional efficacy of these microparticles. In comparison, we also surveyed the expression of these molecules on the surface of the naturally occurred platelet-derived microparticles during 7 days storage of PC. Unlike the previous reports, the results of this study illustrated that the produced IPM retained gpIIb/IIIa molecules. Besides, gpIbα and gpIIb/IIIa were also present on the nPMPs and their levels were significantly decreased during 7 days storage of PCs (P value = 0.001).
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http://dx.doi.org/10.1007/s12288-012-0170-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710554PMC
September 2013

HLA Antigens Shed from the Surface of Synthetic or Naturally Occurred Platelet-Derived Microparticles During Storage of Platelet Concentrate.

Indian J Hematol Blood Transfus 2012 Sep 20;28(3):152-6. Epub 2011 Oct 20.

Research Center, Iranian Blood Transfusion Organization, 14665-1157 Tehran, Iran.

The demand for standard platelet concentrates (PCs) has continued to increase in the recent years. Infusible platelet membranes (IPM) prepared from new or outdated human platelets have been developed as an alternative to standard PCs, with the additional advantage of long shelf life and increased viral safety. Reduction of HLA antigens on the IPM has been assigned as one of the probable advantages of this product. In re-examining this issue, we studied the existence of HLA class I on the surface of IPM microparticles. In comparison we also surveyed HLA expression on the surface of the naturally occurred platelet-derived microparticles (nPMPs) during 7 days storage. Intended for producing IPM, PCs obtained from Iranian blood transfusion organization were lysed; virally inactivated with wet heat in the presence of a heat stabilizer and then sonicated. IPMs were separated using centrifugation and liquid-stored in 4°C. The expression of HLA class I antigens was surveyed using flow cytometry technique. HLA molecules were present on the microparticles. Shedding of HLA antigens was demonstrated from the surface of the both liquid-stored IPM and nPMPs during storage. Storage of IPM in 4°C was accompanied with significant reduction of HLA molecules. It seemed that achievement of HLA-free IPM could be impossible unless chloroquine treated platelets were used to prepare these microvesicles.
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http://dx.doi.org/10.1007/s12288-011-0120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422389PMC
September 2012