In vitro cytotoxic effect of urtica dioica extracts on acute myelogenous leukemia cell line (kg-1)

Background: Urtica dioica is one of the medicinal herbs with many uses in treating various diseases. In some studies, its antiproliferative and apoptotic effects on cancer cell lines have been shown. Therefore, the evaluation of U. dioica effect was performed on KG-1 cell line for acute myelogenous leukemia (AML) for the first time in this study.Materials and Methods: KG-1 cell line was treated by various extracts (aqueous, hydroalcoholic, chloroform and ethyl acetate) of U. dioica aerial parts and roots in different concentrations. Metabolic activity of extracts on cell line was assessed by MTT assay. To evaluate the percentage of apoptotic cells, the flow cytometry was performed by FITC Annexin V-PI apoptosis detection kit in KG-1 cell line treated with root chloroform (UDC-R) and ethyl acetate (UDE-R) extracts. The results have been reported as percentage of cell viability and IC50.Results: Based on MTT results, the strongest IC50 in KG-1 cell line (219.361μg/ml) was related to UDC-R. The flow cytometric analysis showed that UDC-R and UDE-R in IC50 concentration induced early (53.6% and 57.4%, respectively) and late (27% and 33.2%, respectively) apoptosis in KG-1 cells after 24 hrs. The inhibition of cell proliferation by various extracts of U. dioica was dependent on concentration (p=0.000).Conclusion: Flow cytometric analysis confirmed that UDC-R and UDE-R extracts affect on proliferation reduction of KG-1 cells by activating the apoptotic pathway

The Correlation Between SMG1 Promoter Methylation and Its Expression in Acute Lymphoblastic Leukemia Patient

Background: Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of disorders which originate from various important genetic lesions in B and T progenitor cells, including mutations that lead to stage-specific developmental arrest and those that impart the capacity for unlimited self-renewal, resulting in clonal expansion of immature progenitor cells. Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in pediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, and improved supportive. The promoter methylation pattern of DNA in cancer cells is different with the normal cells. Suppressor with morphogenetic effect on genitalia family member (SMG1) belongs to a family of phosphoinositide 3-kinase-related kinases and is the main kinase involved in nonsense-mediated mRNA decay.Materials and Methods: This study was performed to investigate the correlation between SMG1 promotor methylation and its expression levels in acute lymphoblastic leukemia using methylation specific PCR (MSP). Our patients and control samples were collected from Children's Medical Center of children medical center of Imam Khomeini hospital of Tehran. To confirm the MSP results, we used Quantitative Real time-PCR (qRT-PCR ) to measure the expression level of mRNA to find out if there is any relation between pattern of methylation and expression.Results: After performing MSP, we found that SMG1 promoter was hypermethylated. Hyper methylation of SMG1 was detected in 67/74% (21/31) of ALL samples compared to control group. SMG1 mRNA expression was down- regulated 2.74 fold compared to control group.Conclusion: The aim of this study was to investigate the effect of methylation pattern on gene expression. Our findings suggest that SMG1 acts as a functional tumor suppressor gene which was down-regulated by CpG islands hypermethylation in ALL patients. It was shown that the methylation of SMG1 was occurred in the 67/74% of samples

Armeniacae Semen Regulates Apoptosis and Cell Cycle Progression in MCF-7, MDA-MB-231, and T47D Breast Cancer Cell Lines

Background: Amygdalin is a glycoside ingredient of rosacea plants that exerts an antitumor effect by blocking the growth of the tumor cells. Therefore, we aimed to use the Armeniacae semen, a member of the Rosacea family, which contains a large amount of the amygdalin, to evaluate its antiproliferative effect on MCF-7, MDA-MB-231, and T47D breast cancer cell lines. Method: In this experimental study, we prepared the aqueous, ethyl acetate, and hydro-alcoholic extracts of the Armeniacae semen. The MCF-7, MDA-MB-231, and T47D cell lines were treated with different doses of the extracts for 12, 24, 36, and 48 hours; cell viability was investigated with MTT test and cell apoptosis was detected by use of double staining fluorescent. Cell cycle progression was analyzed using a BD Cycle TEST PLUS DNA Kit. We also assessed Bcl2, Bax, and caspase-3 mRNA expression. Results: The best IC50s belonged to hydro-alcoholic extract of the Armeniacae semen in all three cell lines for the 48-hour treatment. We observed a significant increase in Bax and caspase-3 mRNA expression and a noticeable reduction in Bcl2 mRNA compared with the controls. Application of amygdalin to MCF-7, MDA-MB-231, and T47D cell lines increased the number of G0/G1 cells and reduced the number of cells at G2/M phasecompared to the controls. Conclusion: This study showed that the hydro-alcoholic extract of Prunus armeniaca had antitumor effects on breast cancer cell lines as it inhibited the cell cycle at G0/G1 phase and apoptosis induction in the MCF-7, MDA-MB-231, and T47D cell lines

Levels of PM10, PM2.5 and PM1 and Impacts of Meteorological Factors on Particle Matter Concentrations in Dust Events and non Dusty Days

Background: The aim of study was to measure particle matter concentration (PM1, PM2.5 and PM10) during normal, semi-dust and dust-event days. The impacts of some meteorological factors on particle matter concentrations were also investigated.Methods: Samples were collected by Grimm aerosol technik (GmbH model 1/108 Germany) from November 2011 to May 2012. Temperature, humidity, wind speed and UV index were obtaind from the website (www.Weather.ir).Results: The concentration of particulate matter PM1, PM2.5, PM10 in dust event days was 10, 6 and 2 times higher than normal days, respectively. The highest concentration of particle matter was February in winter. There was significant relationship between the particulate matter concentration with temperature and wind speed (P<0.05).Conclusions: The concentration of particulate matter affected by traffic, crowded, humidity and temperature. These factors increased particulate matter concentration specially when was with inversion.

Levels of PM10, PM2.5 and PM1 and Impacts of Meteorological Factors on Particle Matter Concentrations in Dust Events and non Dusty Days

Background: The aim of study was to measure particle matter concentration (PM1, PM2.5 and PM10) during normal, semi-dust and dust-event days. The impacts of some meteorological factors on particle matter concentrations were also investigated.Methods: Samples were collected by Grimm aerosol technik (GmbH model 1/108 Germany) from November 2011 to May 2012. Temperature, humidity, wind speed and UV index were obtaind from the website (www.Weather.ir).Results: The concentration of particulate matter PM1, PM2.5, PM10 in dust event days was 10, 6 and 2 times higher than normal days, respectively. The highest concentration of particle matter was February in winter. There was significant relationship between the particulate matter concentration with temperature and wind speed (P<0.05).Conclusions: The concentration of particulate matter affected by traffic, crowded, humidity and temperature. These factors increased particulate matter concentration specially when was with inversion.

Priority Setting for Improvement of Cervical Cancer Prevention in Iran

Background: Cervical cancer is the fourth most common cancer among women worldwide. Organized cervical screening and vaccination against human papilloma virus (HPV) have been successful interventions for prevention of invasive cervical cancer (ICC). Because of cultural and religious considerations, ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention of ICC in this setting. Methods: We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go-zone analysis to determine final list of priorities for ICC prevention in Iran. Results: From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management of precancerous lesions. In addition, we emphasized considering insurance coverage for cervical screening, public awareness, and research priorities, and establishment of a cervical screening registry. Conclusion: A comprehensive approach and implementation of organized cervical screening program is necessary for prevention of ICC in Iran and other low incidence Muslim countries. Because of high cost for vaccination and low incidence of cervical cancer, we do not recommend HPV vaccination for the time being in Iran

Interpretation of erythrocyte histograms obtained from automated hematology analyzers in hematologic diseases

Background: Presently, the graphical data of blood cells (histograms and cytograms or/ scattergrams) that they are usually available in all modern automated hematology analyzers are an integral a part of automated complete blood count (CBC). To find incorrect results from automated hematology analyzer and establish the samples that require additional analysis, Laboratory employees will use those data for quality control of obtaining results, to assist identification of complex and troublesome cases. Methods: During this descriptive analytic study, in addition to erythrocyte graphs from variety of patients, referring from March 2013 to Feb 2014 to our clinical laboratory, Zagros Hospital, Kermanshah, Iran, are given, the papers published in relevant literature as well as available published manuals of automatic blood cell counters were used. articles related to the key words of erythrocyte graphs and relevant literature as well as available published manuals of automatic blood cell counters were searched from valid databases such as Springer Link, google scholar, Pubmed and Sciencedirect. Then, the articles related to erythrogram, erythrocyte histogram and hematology analyzer graphs are involved in diagnosis of hematological disorder were searched and selected for this study. Results: Histograms and different automated CBC parameter become abnormal in various pathologic conditions, and can present important clues for diagnosis and treatment of hematologic and non-hematologic disorders. In several instances, these histograms have characteristic appearances in an exceedingly wide range of pathological conditions. In some hematologic disorders like iron deficiency or megaloblastic anemia, a sequential histogram can clearly show the progressive treatment and management. Conclusion: These graphical data are often accompanied by other automated CBC parameter and microscopic examination of peripheral blood smears (PBS), and can help in monitoring and interpretation of abnormal morphological changes. In the diagnosis and monitoring of anemias, analysis of histograms could also be considered as a new parameter in the combine with red blood cell indices. Histograms ought to use as a screening tool, and not considered diagnostic for pathological conditions

Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia

Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced expression of microRNA-192 (miR-192) has been detected in many cancers. In this study, we investigated the role of miR-192 in cell proliferation and cell cycle control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL). Cell cycle analysis by DNA content using propidium iodide staining and cell apoptosis analysis using Annexin V assay were carried out. Cell proliferation changes were monitored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene expression were determined by quantitative reverse transcription PCR. Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells. After 72 and 96 hours of transduction, apoptosis was significantly increased in the cells transduced with miR-192-overexpressing virus compared with control cells. The expression of P53, BAX, and CASP3 increased after 48 hours of transduction in miR-192-overexpressing cells, but no change was observed in BCL-2 expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the cells overexpressing miR-192 compared with controls. The results of our study suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells

Assesment Of The Efficacy Of HESA-A On The Proliferation And Apoptosis Of Chronic Myelogenous Leukemia Cell Line(K562)

Background and Aim: Chronic myelogenous leukemia is characterized by Philadelphia (Ph) chromosome, the presence of BCR-ABL fusion gene and constitutive activation of the ABL1 tyrosine kinase. Despite an excellent result of target therapy by imatinib, some patients develop resistance to imatinib. In this study Efficacy of HESA-A on proliferation and apoptosis of K562 cell line was assessed. Materials and Methods: In this study doubling time of K562 cell line was calculated. The cells were affected by various concentrations of HESA-A(1,2,4 and 8 mg/ml respectively). Cytotoxicity and IC50 dose of HESA-A were detected by MTT and trypan blue exclusion assay. Apoptosis was assessed by flowcytometry after 48 h cell treatment in the presence of IC50 dose. Results: Doubling time of K562 cells was 24 hours. HESA-A reduced the number of viable K562 cells in a concentration dependent manner.IC50 dose was 3.5 mg/ml. In flowcytometry analysis of apoptosis, 19.22% of the treated cells were located in the position of the necrotic cells. Conclusion: The results of MTT and trypan blue exclusion assay suggest that HESA-A inhibits the growth of k562 cells in a concentration dependent manner and induces necrosis in K562 cells

Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery

Conventional chemotherapy, one of the most widely used cancer treatment methods, has serious side effects, and usually results in cancer treatment failure. Drug resistance is one of the primary reasons for this failure. The most significant drawbacks of systemic chemotherapy are rapid clearance from the circulation, the drug's low concentration in the tumor site, and considerable adverse effects outside the tumor. Several ways have been developed to boost neoplasm treatment efficacy and overcome medication resistance. In recent years, targeted drug delivery has become an essential therapeutic application. As more mechanisms of tumor treatment resistance are discovered, nanoparticles (NPs) are designed to target these pathways. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation. Nano-drugs have been increasingly employed in medicine, incorporating therapeutic applications for more precise and effective tumor diagnosis, therapy, and targeting. Many benefits of NP-based drug delivery systems in cancer treatment have been proven, including good pharmacokinetics, tumor cell-specific targeting, decreased side effects, and lessened drug resistance. As more mechanisms of tumor treatment resistance are discovered, NPs are designed to target these pathways. At the moment, this innovative technology has the potential to bring fresh insights into cancer therapy. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation.Ministerio de Ciencia e Innovación (MICIN)Agencia Estatal de InvestigaciónUnión EuropeaUniversidad Complutense de MadridDepto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu