Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.
Jafarzadeh-Kashi, Tahereh Sadat;Mirzaii, Marzieh;Erfan, Mohmmad;Fazel, Akbar;Eskandarion, Solmaz;Rakhshan, Vahid
The Journal of Advanced Prosthodontics
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v.3
no.4
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pp.216-220
/
2011
PURPOSE. Heat of composite polymerization (HP) indicates setting efficacy and temperature increase of composite in clinical procedures. The purpose of this in vitro experimental study was to evaluate the effects of 5 temperatures on HP of two new composites. MATERIALS AND METHODS. From each material (Core Max II [CM] and King Dental [KD]), 5 groups of 5 specimens each were prepared and their total HPs (J/gr) were measured and recorded, at one of the constant temperatures $0^{\circ}C$, $15^{\circ}C$, $23^{\circ}C$, $37^{\circ}C$ and $60^{\circ}C$ ($2{\times}5{\times}5$ specimens) using a differential scanning calorimetry (DSC) analyzer. The data were analyzed using a two-way ANOVA, a Tukey's test, an independent-samples ttest, and a linear regression analysis (${\alpha}=0.05$). RESULTS. No polymerization reactions occurred at $0^{\circ}C$; then this temperature was excluded from statistical analyses. The mean HP of the remaining 20 KD specimens was $20.5{\pm}14.9$ J/gr, while it was $40.7{\pm}12.9$ J/gr for CM. The independent-samples t-test showed that there were significant differences between the HP of the two materials at the temperatures $15^{\circ}C$ (P=.0001), $23^{\circ}C$ (P=.0163), $37^{\circ}C$ (P=.0039), and $60^{\circ}C$ (P=.0106). Linear regression analysis showed statistically significant correlations between environment temperatures and HP of CM ($R^2=0.777$). CONCLUSION. Using CM is advantageous over conventional composite because of its better polymerization capacity. However due to its high HP, further studies should assess its temperature increase in vivo. Preheating KD is recommended. Refrigerating composites can negatively affect their polymerization potential.
Shafiee, Sayed Mohammad;Rasti, Mozhgan;Seghatoleslam, Atefeh;Azimi, Tayebeh;Owji, Ali Akbar
Asian Pacific Journal of Cancer Prevention
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v.16
no.9
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pp.3723-3727
/
2015
The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however, the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53. By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and after cell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1 transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpression of UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve direct interaction of UBE2Q1with p53.
Azimi, Ako;Hagh, Majid Farshdousti;Talebi, Mehdi;Yousefi, Bahman;feizi, Abbas Ali Hossein pour;Baradaran, Behzad;Movassaghpour, Ali Akbar;Shamsasenjan, Karim;Khanzedeh, Taghi;Ghaderi, Abdol Hasan;Heydarabad, Milad Zadi
Asian Pacific Journal of Cancer Prevention
/
v.16
no.15
/
pp.6463-6468
/
2015
Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.
The present research was undertaken to monitor the effects of restricted and ad. libitum feeding during last trimester of pregnancy on the performance of crossbred dairy cows and their calves. For this purpose two groups of crossbred cows having eight animals in each group were put into two plane of nutrition during their last three months of pregnancy. Dietary energy level in one group was calculated as per Ministry of Agriculture, Fisheries and Food, (MAFF, UK) and the cows on other group received ad. libitum feeding (concentrate level similar to MAFF, recommendation+ad. libitum roughage). After calving, the cows of both groups were given same diet (ad. libitum) to study the effect of feeding during pregnancy on subsequent lactation performance of the cows. It was observed that during pre-calving period cows on ad. libitum feeding gained significantly (p<0.05) more body weight than that of cows on restricted feeding ($38.50{\pm}6.04$ vs $21.37{\pm}8.04kg/cow$). There was no significant differences between the birth weight of calves of restricted ($21.31{\pm}2.18kg$) and ad. libitum ($20.31{\pm}3.27kg$) groups. Dietary energy intake of ad. libitum group ($50.22{\pm}4.24$ MJ ME/d/cow) was significantly higher (p<0.01) than that of restricted group ($39.76{\pm}1.03$ MJ ME/d/cow). During lactation period cows that were on restricted feeding produced little more milk (3.06 lit/cow/day), than that of the cows on ad. libitum feeding (2.84 lit/cow/day). Although growth rate of the calves of restricted group upto one month ($0.23{\pm}0.09kg/calf/d$) was significantly (p<0.01) higher than that of ad. libitum group ($0.17{\pm}0.08kg/calf/d$) but after four months the growth rate of the calves of two groups become nearly similar ($0.35{\pm}0.02$ vs $0.37{\pm}0.03kg/calf/d$) and difference between them was non-significant. During lactation period cows of restricted group gained little weight but cows of ad. libitum group lost significantly (p<0.05) more weight. Per day metabolizable energy intake in both group during lactation period was nearly similar (67.54 vs 69.58 MJ ME). It is concluded that ad. libitum feeding during last trimester of pregnancy is neither economic for getting maximum milk yield nor for calf growth rate and MAFF, recommended level of dietary energy during that period could be applied on our pregnant crossbred dairy cows.
Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.
Hedayatizadeh-Omran, Akbar;Rafiei, Alireza;Alizadeh-Navaei, Reza;Tehrani, Mohsen;Valadan, Reza;Moradzadeh, Kambiz;Panbechi, Mohammad;Taghavi, Seyed Mehdi
Asian Pacific Journal of Cancer Prevention
/
v.16
no.4
/
pp.1431-1434
/
2015
Background: Breast cancer is one of the most common cancers among women worldwide and the HER2 receptor plays an important role in its development and progression. This systematic review aimed to summarize the role of HER2 in brain metastasis in patients with breast cancer. Materials and Methods: We conducted a literature search by advanced search in title field using the Scopus, Pubmed, and Google scholar databases until the end of June 2014. With metastasis, metastatic, HER2, brain, and breast cancer, as terms of search we selected 31 articles, which were reviewed by two independent and blinded expert reviewers. The studies were first selected according to their titles and abstracts. Quality of the studies were then assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) protocol for observational studies and CONSORT(Consolidation of Standards for Reporting Trials) protocol for clinical trials. For statistical analyses, we used STATA, version 11.0 software. Forest and funnel diagrams were drawn and for heterogeneity, index was also considered. Also we used meta regression analysis. Results: Finally, we reviewed 10 studies. The prevalence of brain metastasis in HER2-positive breast cancer patients was 24.9%. There was publication bias in the reviewed studies. Meta regression analysis showed that follow up time had no significant effect (p=0.396) on the prevalence of brain metastasis. Conclusions: The results showed a high prevalence of brain metastasis in HER2 positive breast cancer patients.
Shishodia, Nitin Pratap;Divakar, Darshan Devang;Al Kheraif, Abdulaziz Abdullah;Ramakrishnaiah, Ravikumar;Pathan, Akbar Ali Khan;Parine, Narasimha Reddy;Chandroth, Santhosh Vediyera;Purushothaman, Binu
Asian Pacific Journal of Cancer Prevention
/
v.16
no.3
/
pp.1255-1258
/
2015
Background: Locally advanced head and neck cancer is generally incurable and has a short survival rate. This study aimed to evaluate symptom relief, disease response, and acute toxicity after palliative hypo-fractionated radiotherapy and long-term survival in affected patients. Materials and Methods: Between January 2011 to December 2011, 80 patients who were histopathologically diagnosed as having stage III or stage IV head and neck squamous cell carcinoma based on Eastern Cooperative Oncology Group (ECOG) performance status 1-3, were offered palliative radiotherapy (20 Gy/5Fr/5 Days). Later these patients were evaluated on 30th day after completion of treatment for disease response based on World Health Organisation (WHO) criteria and palliation of symptoms using symptomatic response grading and acute toxicities by the Radiation Therapy Oncology Group (RTOG). Many patients were given post radiation therapy (RT) palliative chemotherapy for appropriate palliative care and a few patients were selected for further curative RT. The overall survival was also evaluated among this group of patients with last follow up date of 1st May, 2014. Results: The most common presenting complaint was pain followed by dysphagia. Most patients (60-70%) had appreciable relief in their presenting symptoms. A good response was observed in the majority following palliative RT; a few patients had progressive disease and some had stable and regressed disease. None of the patients experienced radiation toxicity that required hospital admission. Almost all showed grade one and two acute skin and mucosal toxicity one month after completion of treatment. The mean survival days for patients given only hypofractionated palliative RT was 307 days, those with post palliative RT and palliative chemotherapy was 390 days and patients who went on to receive further palliative RT and curative RT dose had significantly overall survival of 582 days. Conclusions: Advanced head and neck cancer should be identified for suitable palliative hypofractionated radiotherapy to achieve acceptable symptom relief in a great proportion of patients and should be followed by palliative chemotherapy or curative RT in suitable cases for long-term symptom-free survival.
Mansouri-Torshizi, Hassan;Saeidifar, Maryam;Ghasemi, Zahra Yekke;Khastan, Mahmood;Divsalar, Adeleh;Saboury, Ali Akbar
Journal of the Korean Chemical Society
/
v.55
no.1
/
pp.70-80
/
2011
Two new palladium (II) complexes, [Pd (phen)(pip-dtc)]$NO_3$ and [Pd(phen)(mor-dtc)]$NO_3$, (where phen is 1,10-Phenantroline, pip-dtc is piperidinedithiocarbamate anion and mor-dtc is morpholinedithiocarbamate anion) have been synthesized and characterized by elemental analysis, spectroscopic studies (FT-IR, $^1H$ NMR, UV-Vis) and conductance measurement. In these complexes, the dithiocarbamate ligands coordinate with Pd (II) center as bidentate with two sulfur atoms. These two complexes have been tested against chronic myelogenous leukemia cell line, K562. They show $IC_{50}$ values less than cisplatin and thus the mode of binding of the complexes to calf thymus DNA (CT-DNA) were investigated by ultraviolet difference and fluorescence spectroscopy. They can denature DNA, exhibit cooperative binding and intercalate into DNA. Several binding and thermodynamic parameters are also described.
Glycerol is a non-volatile compound with no aromatic properties that contributes significantly to the quality of wine by providing sweetness and richness of taste. In addition, it is also the third most significant byproduct of alcoholic fermentation in terms of quantity after ethanol and carbon dioxide. In this study, Fourier transform infrared (FT-IR) spectroscopy was employed as a fast non-destructive method in conjugation with multivariate regression analysis to build a model for the quantitative analysis of glycerol concentration in wine samples. The samples were prepared by using three varieties of red wine samples (i.e., Shiraz, Merlot, and Barbaresco) that were adulterated with glycerol in concentration ranges from 0.1 to 15% (v·v-1), and subjected to analysis together with pure wine samples. A net analyte signal (NAS)-based methodology, called hybrid linear analysis in the literature (HLA/GO), was applied for predicting glycerol concentrations in the collected FT-IR spectral data. Calibration and validation sets were designed to evaluate the performance of the multivariate method. The obtained results exhibited a high coefficient of determination (R2) of 0.987 and a low root mean square error (RMSE) of 0.563% for the calibration set, and a R2 of 0.984 and a RMSE of 0.626% for the validation set. Further, the model was validated in terms of sensitivity, selectivity, and limits of detection and quantification, and the results confirmed that this model can be used in most applications, as well as for quality assurance.
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