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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Osteopontin,Splice isoforms,Leukemia,Solid Tumor,Angiogenesis
- چکیده:
- چکیده انگلیسی: Osteopontin (OPN) is a glycoprotein involved in regulation of various influences on tumor progression, such as
cellular proliferation, apoptosis, angiogenesis, and metastasis. Vascular endothelial growth factor (VEGF) is a secreted
molecule supporting angiogenesis in various cancers through activation of the PI3K/AKT/ERK1/2 pathway. OPN and
VEGF have a number of isoforms with various activities. In spite of the well-defined association between OPN and
VEGF isoform expression and cure rate for solid tumors, there is a scarcity of information as to any association in
leukemia. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that OPN and VEGF
isoform expression levels may impact on chemoresistance and relapse in leukemia the same as in solid tumors. Hence,
the aim of our review was to explain relationships between OPN and VEGF isoforms and angiogenesis and related
pathways in chemoresistance of leukemia and solid tumors. Our findings demonstrated that OPNb and OPNc alongside
with VEGF isoforms and other gene pathways are involved in angiogenesis and also might promote chemoresistance
and even recurrence in leukemia and solid tumors. To sum up, targeting OPN isoforms, particularly b and c, might be
a novel therapeutic strategy for the treatment of leukemia as well as solid tumors.- انتشار مقاله: 22-09-1396
- نویسندگان: Akram Mirzaei,Saeed Mohammadi*,Seyed Hamid Ghaffari,Marjan Yaghmaie,Mohammad Vaezi,Kamran Alimoghaddam,Ardeshir Ghavamzadeh
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Osteopontin,Chemoresistance,Anti-angiogenesis
- چکیده:
- چکیده انگلیسی:
Osteopontin (OPN) is an extracellular structural protein that is secreted by osteoblasts and hematopoietic cells. It suppresses the proliferation of hematopoietic stem and also plays an important role in promoting survival and drug resistance in leukemic stem cells (LSCs). Since the role of OPN isoforms in AML angiogenesis are remaining controversial, in the present study, we aimed to evaluate whether curcumin (CUR), as a known natural component with anti-angiogenesis effects, in a combination of AML conventional regiment has the potency to preclude induced anti-angiogenesis effects of OPN isoforms or not? Leukemia cells were treated with different concentration of CUR and AML conventional drugs alone and/or in combination with together to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and mRNA levels of OPN isoforms and AKT/ VEGF-A and VEGF-C/ STAT3/ β-catenin/ CXCR4/ IL-6/ KDR gene expression were investigated by Real Time-PCR method. Moreover, to confirm OPN gene expression data, we investigated the effect of simvastatin and OPN siRNA as an OPN inhibitor on the cell proliferation and induction of apoptosis in the indicated cell lines. Our data display that Ara-c (2μM and 1μM in KG-1 and U937 cell lines respectively), CUR (40μM in both cell lines), and also their combination significantly increased the percentage of apoptotic cells. Moreover, the mRNA level of OPN isoforms were down regulated in the KG-1and U937 cell lines treated with Ara-c while, upregulated in KG-1and U937 cell lines treated with CUR and its combination. Our results suggest that despite anti-angiogenesis effects of CUR, AML cells probably evade from anti-angiogenesis effects of CUR via induction of OPN b and c isoform and related molecular pathways.- انتشار مقاله: 11-05-1396
- نویسندگان: Akram Mirzaei,Seyed Hamid Ghaffari,Mohsen Nikbakht,Hosein Kamranzadeh Foumani,Mohammad Vaezi,Saeed Mohammadi,Kamran Alimoghaddam,Ardeshir Ghavamzadeh
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Osteopontin,Chemoresistance,Anti-angiogenesis
- چکیده:
- چکیده انگلیسی:
Osteopontin (OPN) is an extracellular structural protein that is secreted by osteoblasts and hematopoietic cells. It suppresses the proliferation of hematopoietic stem and also plays an important role in promoting survival and drug resistance in leukemic stem cells (LSCs). Since the role of OPN isoforms in AML angiogenesis are remaining controversial, in the present study, we aimed to evaluate whether curcumin (CUR), as a known natural component with anti-angiogenesis effects, in a combination of AML conventional regiment has the potency to preclude induced anti-angiogenesis effects of OPN isoforms or not? Leukemia cells were treated with different concentration of CUR and AML conventional drugs alone and/or in combination with together to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and mRNA levels of OPN isoforms and AKT/ VEGF-A and VEGF-C/ STAT3/ β-catenin/ CXCR4/ IL-6/ KDR gene expression were investigated by Real Time-PCR method. Moreover, to confirm OPN gene expression data, we investigated the effect of simvastatin and OPN siRNA as an OPN inhibitor on the cell proliferation and induction of apoptosis in the indicated cell lines. Our data display that Ara-c (2μM and 1μM in KG-1 and U937 cell lines respectively), CUR (40μM in both cell lines), and also their combination significantly increased the percentage of apoptotic cells. Moreover, the mRNA level of OPN isoforms were down regulated in the KG-1and U937 cell lines treated with Ara-c while, upregulated in KG-1and U937 cell lines treated with CUR and its combination. Our results suggest that despite anti-angiogenesis effects of CUR, AML cells probably evade from anti-angiogenesis effects of CUR via induction of OPN b and c isoform and related molecular pathways.- انتشار مقاله: 11-05-1396
- نویسندگان: Akram Mirzaei,Seyed Hamid Ghaffari,Mohsen Nikbakht,Hosein Kamranzadeh Foumani,Mohammad Vaezi,Saeed Mohammadi,Kamran Alimoghaddam,Ardeshir Ghavamzadeh
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Osteopontin,Chemoresistance,Anti-angiogenesis
- چکیده:
- چکیده انگلیسی:
Osteopontin (OPN) is an extracellular structural protein that is secreted by osteoblasts and hematopoietic cells. It suppresses the proliferation of hematopoietic stem and also plays an important role in promoting survival and drug resistance in leukemic stem cells (LSCs). Since the role of OPN isoforms in AML angiogenesis are remaining controversial, in the present study, we aimed to evaluate whether curcumin (CUR), as a known natural component with anti-angiogenesis effects, in a combination of AML conventional regiment has the potency to preclude induced anti-angiogenesis effects of OPN isoforms or not? Leukemia cells were treated with different concentration of CUR and AML conventional drugs alone and/or in combination with together to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and mRNA levels of OPN isoforms and AKT/ VEGF-A and VEGF-C/ STAT3/ β-catenin/ CXCR4/ IL-6/ KDR gene expression were investigated by Real Time-PCR method. Moreover, to confirm OPN gene expression data, we investigated the effect of simvastatin and OPN siRNA as an OPN inhibitor on the cell proliferation and induction of apoptosis in the indicated cell lines. Our data display that Ara-c (2μM and 1μM in KG-1 and U937 cell lines respectively), CUR (40μM in both cell lines), and also their combination significantly increased the percentage of apoptotic cells. Moreover, the mRNA level of OPN isoforms were down regulated in the KG-1and U937 cell lines treated with Ara-c while, upregulated in KG-1and U937 cell lines treated with CUR and its combination. Our results suggest that despite anti-angiogenesis effects of CUR, AML cells probably evade from anti-angiogenesis effects of CUR via induction of OPN b and c isoform and related molecular pathways.- انتشار مقاله: 11-05-1396
- نویسندگان: Akram Mirzaei,Seyed Hamid Ghaffari,Mohsen Nikbakht,Hosein Kamranzadeh Foumani,Mohammad Vaezi,Saeed Mohammadi,Kamran Alimoghaddam,Ardeshir Ghavamzadeh
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Osteopontin,Leukemis Stem Cells,Chemoresistance
- چکیده:
- چکیده انگلیسی: Despite impressive advances in the therapeutic approches, the long-term survival rate of acute myeloid leukemia (AML) is considered to be significantly low as a result of resistance to the treatment and desease relapse. Among multitude oncogenic proteins invovlved in aquisition of chemo-resistance phenotype, osteopontin (OPN) recently attracted tremendous attentions. In spite of the well-defined association between OPN expression and cure rate in solid tumors, there is a scarcity of analysis on the role of this protein in AML. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that the high expression of OPN isoforms may participate in disrupting the regulation of apoptosis in AML cells and it s relapse. To investigate the association between induction of apoptosis and OPN isoform expression, two distinct AML cell lines (KG-1 as a leukemic stem cell model and U937) were treated with chemotherapy drugs and the cell viability and apoptosis were evaluated by MTT and annexin/PI assay. After determination suitable drugs doses, the mRNA expression level of OPN and OPN-related genes were investigated. Our results demonstrated for the first time that the acquired up-regulation of OPN-b and c isoforms might prevent conventional chemotherapy regimen-induced apoptosis in AML cells. Moreover, the resulting data revealed that up-pregulation of OPN-b and c in AML cells was concurrently associated with the up-regulation of AKT, VEGF, CXCR4, STAT3 and IL-6 expression. To sum up, this study suggest that OPN-b and c isoforms could be considered as a unique beneficial molecular biomarker which is associated with chemoresistance. Hence, this isoforms are considerable as a potential moleculare candidate for detection of minimal residual disease (MRD) and determination of remission in AML patients. Furthure evaluation with quantative Real tim PCR on patient sample to comfim this finding seems to be be nessesary.
- انتشار مقاله: 07-03-1396
- نویسندگان: Akram Mirzai,Saeed Mohammadi,Seyed Hamid Ghaffari,Davood Bashash,Mohsen Nikbakht,Marjan Yaghmaie,Kamran Alimoghaddam,Ardeshir Ghavamzadeh
- مشاهده