排序方式: 共有11条查询结果,搜索用时 31 毫秒
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Mahban Irandoust Julian Alvarez Zarate Isabelle Hubeek Ellen M. van Beek Karin Schornagel Aart J. F. Broekhuizen Mercan Akyuz Arjan A. van de Loosdrecht Ruud Delwel Peter J. Valk Edwin Sonneveld Pamela Kearns Ursula Creutzig Dirk Reinhardt Eveline S. J. M. de Bont Eva A. Coenen Marry M. van den Heuvel-Eibrink C. Michel Zwaan Gertjan J. L. Kaspers Jacqueline Cloos Timo K. van den Berg 《PloS one》2013,8(1)
Background
Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPα) on macrophages. Although AML cells express SIRPα, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPα in acute myeloid leukemia.Design and Methods
We analyzed the expression of SIRPα, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPα on two low SIRPα expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPα expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs.Results
By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPα is differentially expressed in AML subgroups and its expression level is dependent on differentiation stage, with high levels in FAB M4/M5 AML and low levels in FAB M0–M3. Interestingly, AML patients with high SIRPα expression had a poor prognosis. Our results also showed that SIRPα is upregulated upon differentiation of NB4 and Kasumi cells. In addition, triggering of SIRPα with an agonistic antibody in the cells stably expressing chimeric SIRPα, led to inhibition of growth and induction of programmed cell death. Finally, the SIRPα-derived signaling synergized with the activity of established antileukemic drugs.Conclusions
Our data indicate that triggering of SIRPα has antileukemic effect and may function as a potential therapeutic target in AML. 相似文献2.
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Nobakht-Haghighi Navid Rahimifard Mahban Baeeri Maryam Rezvanfar Mohammad Amin Moini Nodeh Shermineh Haghi-Aminjan Hamed Hamurtekin Emre Abdollahi Mohammad 《Molecular and cellular biochemistry》2018,449(1-2):267-276
Molecular and Cellular Biochemistry - Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study... 相似文献
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Mitra Ghasemi-Chaleshtari Seyed Hossein Kiaie Mahzad Irandoust Hadis Karami Mohsen Nabi Afjadi Sepideh Ghani Nasimeh Aghaei Vanda Mohammad Javad Ghaderi Sede Armin Ahmadi Ali Masjedi Hadi Hassannia Fatemeh Atyabi Mohammad Hojjat-Farsangi Afshin Namdar Ghasem Ghalamfarsa Farhad Jadidi-Niaragh 《Journal of cellular physiology》2020,235(12):10068-10080
Inhibitory immune checkpoint (ICP) molecules are important immunosuppressive factors in a tumor microenvironment (TME). They can robustly suppress T-cell-mediated antitumor immune responses leading to cancer progression. Among the checkpoint molecules, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is one of the critical inhibitors of anticancer T-cell responses. Besides, the expression of adenosine receptor (A2AR) on tumor-infiltrating T cells potently reduces their function. We hypothesized that concomitant silencing of these molecules in T cells might lead to enhanced antitumor responses. To examine this assumption, we purified T cells from the tumor, spleen, and local lymph nodes of CT26 colon cancer-bearing mice and suppressed the expression of A2AR and CTLA-4 using the small interfering RNA (siRNA)-loaded polyethylene glycol-chitosan-alginate (PCA) nanoparticles. The appropriate physicochemical properties of the produced nanoparticles (NPs; size of 72 nm, polydispersive index [PDI] < 0.2, and zeta potential of 11 mV) resulted in their high efficiency in transfection and suppression of target gene expression. Following the silencing of checkpoint molecules, various T-cell functions, including proliferation, apoptosis, cytokine secretion, differentiation, and cytotoxicity were analyzed, ex vivo. The results showed that the generated nanoparticles had optimal physicochemical characteristics and significantly suppressed the expression of target molecules in T cells. Moreover, a concomitant blockade of A2AR and CTLA-4 in T cells could synergistically enhance antitumor responses through the downregulation of PKA, SHP2, and PP2Aα signaling pathways. Therefore, this combination therapy can be considered as a novel promising anticancer therapeutic strategy, which should be further investigated in subsequent studies. 相似文献
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Ranjzad F Mahmoudi T Irani Shemirani A Mahban A Nikzamir A Vahedi M Ashrafi M Gourabi H 《Molecular biology reports》2012,39(3):2313-2319
In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH),
and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including
181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR
gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the
VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between
the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before
or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with
“TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in
women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings
suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for
the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms
and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations. 相似文献
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Faheem Maqbool Haji Bahadar Shokoufeh Hassani Kamal Niaz Maryam Baeeri Mahban Rahimifard Seyedeh Farnaz Ghasemi-Niri Mohammad Abdollahi 《Journal of cellular biochemistry》2019,120(9):16195-16205
Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators’ cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals. 相似文献
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Biomechanics and Modeling in Mechanobiology - Fluid flow in (porous) bone plays an important role in its maintenance, adaptation, and healing after an injury. Experimental and computational studies... 相似文献