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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,Arsenic trioxide,Thalidomide,Vascular Endothelial Growth Factor (VEGF)
- چکیده:
- چکیده انگلیسی: Acute myeloid leukemia (AML) is a blood disorder characterized by uncontrolled proliferation of myeloid
progenitors and decrease in the apoptosis rate. The vascular endothelial growth factor (VEGF) promotes blood vessel
regeneration which might play important roles in development and progression of neoplasia. Our previous studies
focused on cytotoxicity and anticancer effects of arsenic trioxide (ATO) and thalidomide (THAL) as an anti-VEGF
compound in the AML cell model. ATO also affects regulatory genes involved in cell proliferation and apoptosis. The
aim of present study was to examine the effects of ATO and THAL alone and in combination on U937 and KG-1 cells
, with attention to mRNA expression for VEGF isoforms. Growth inhibitory effects was assessed by MTT assay and
apoptosis induction was determined by Annexin/PI staining. mRNA expression levels were evaluated by real-time
PCR. Our data indicated that ATO (1.618μM and 1μM in KG-1 and U937 cell lines respectively), THAL (80μM and
60μM) and their combination inhibited proliferation and induced apoptosis in our cell lines. mRNA expression of
VEGF (A, B) decreased while C and D isoforms did not show any significant changes. Taken together, according to
the obtained results, the VEGF autocrine loop could be a target as a therapeutic strategy for cases of AML.- انتشار مقاله: 14-10-1396
- نویسندگان: Mahnaz Mohammadi Kian,Saeed Mohammadi,Mahmoud Tavallaei,Bahram Chahardouli,Saharbano Rostami,Mahdi Zahedpanah,Ardeshir Ghavamzadeh,Mohsen Nikbakht
- 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
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: acute myeloid leukemia,AML,VEGF,sorafenib,Arsenic trioxide,Cell lines
- چکیده:
- چکیده انگلیسی:
Acute myeloid leukemia (AML), is a clonal disorder caused by acquired somatic mutations and chromosomal rearrangements. According to some evidence, progression of hematolymphoid malignancies depends on the induction of new blood vessel formation under the influence of acute leukemia. Various factors are produced by cancer cells under hypoxic conditions to increase vascular formation. Among these, vascular endothelial growth factor (VEGF) plays a crucial role. Cytotoxicity and anticancer effects of arsenic trioxide (ATO) have been reported in many cancers. Sorafenib, known as an angiogenic inhibitor, decreases leukemic cell survival. The aim of this study was to indicate combination effects of ATO and sorafenib in two AML cell lines, KG-1 and U937. Effective doses was determined by MTT assay for both single and combination treatments. Percentages of apoptotic cells were evaluated by Annexin V FITC staining and mRNA levels of VEGF isoforms and receptor expression were investigated by Real-Time PCR. Our data show that sorafenib (5μM and 7μM in KG-1 and U937 cell lines respectively), ATO (1.618μM and 1μM in KG-1 and U937 cell lines respectively), and also their combination significantly increased the percentage of apoptotic cells. In addition the mRNA level of VEGF isoforms was downregulated in the U937 cell line while upregulated in KG-1 cells. Taken together, our results suggest that the VEGF autocrine loop may have an influence on AML development and progression and could be consider as a therapeutic target. The combination of sorafenib as a VEGF inhibitor with ATO synergistically inhibits cell proliferation and promotes apoptosis.- انتشار مقاله: 13-02-1396
- نویسندگان: Atousa Haghi,Saeed Mohammadi,Masoumeh Heshmati,Ardeshir Ghavamzadeh,Mohsen Nikbakht
- مشاهده