The roles of DNA epigenetics and clinical significance in Chronic Myeloid Leukemia: a review.

Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22) (q34;q11.2) encoding for the BCR-ABL fusion oncogene. Growing body of evidence suggests that epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukemic clone escape and disease propagation. The significant of therapeutic role in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms.  This article focused on the CML and epigenetic and clinical significance. An electronic search of peer-reviewed articles was systematically performed to obtain the relevant literature with the CINAHL, cancer, Google scholar, self-experience and PubMed databases. The keywords included leukemia, cancer, illness, epigenetic. The inclusion criteria for the reviews were that the documents were original quantitative research and published in English. Articles that were not directly relevant to the present objective were excluded. Current progress in molecular biology and bioinformatics offer novel promising experiments namely as next generation sequencing for new development in epigenetic figures characterization and more understanding of the epigenetic mechanisms to be successfully utilized for personalized CML therapy in the next coming years.

Cytotoxicity Effects of Mouse IgG Produced against Three Nanoliposomal Human DR5 Receptor Epitopes on Breast Cancer Cells.

Cancer causes cells to avoid death while being the second cause of death in the world itself. Damaged cells in the absence of apoptosis will increasingly amplify their inefficient genome. Of the two main apoptosis inducing pathways in cells, the first has p53 protein as the main initiating factor in the cascade. According to research results this protein s mutated in 50% of cancers and sointerest has cooncentrated on the second pathway that features death receptors. Among these receptors TRAIL1/DR5 is especially expressed in cancer cells. So targeting such receptors can initiate the apoptotic cascade in cells. Interestingly by substitution of activating ligands with antibodies as agonists, we could efficiently turn on the apoptosis pathway. First of all, three small peptides from the DR5 protein extracellular domain were synthesized and injected with two different kind of adjuvants (Fround and liposomal encapsulation) separately into mice at 15 day intervals. As a result, liposomal peptides induced the immune system more efficient than Frounds adjuvant and at the end point the antibodies which were obtained from liposomal peptide injection induced much more effective death. Liposomal formol could be used as an adjuvant in immunization utilizing small peptides. They carry, protect and deliver peptides very efficiently. In addition, small peptides of a certain size from the extracellular domain of DR5 proteins not only can induce immune system but also produce antibodies playing a remarkable anti-cancer roles against breast cancer cells (MCF-7).

Overexpression of the MUC1 Gene in Iranian Women with Breast Cancer Micrometastasis.

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining. The evaluation of tumor and normal samples for expression of MUC1 gene, the results were 49.1% non-expressive and 45.3% expression (Student t, p = 0.03). Also in comparison of normal breast tissue and breast cancer SLN for MUC1 gene, MUC1 negative SLNs were 75.0% (18 samples) and MUC1 positive samples were 25.0% (6 samples). Over-expression of MUC1 gene may offer a target for therapy related to progression and metastasis in women with breast cancer.

Apoptotic Killing of Breast Cancer Cells by IgYs Produced Against a Small 21 Aminoacid Epitope of the Human TRAIL-2 Receptor.

TRAIL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand belongs to one of important cytokine superfamilIES, tumor necrosis factor (TNFα) . TRAIL-2 receptor agonists activate several cell signaling pathways in cells in different manners and could lead to apoptosis or necrosis. Agonistic egg yolk antibodies like IgY which have been developed in a selective manner could activate TRAIL death receptors such as TRAIL-2 (DR5) and thus apoptosis signaling. We here investigated induction of apoptosis in human breast cancer cells (MCF7 cell line) by an IgY produced against an 21 aminoacid epitope of the human TRAIL-2 receptor. As the first step a small peptide of 21 aminoacids choosen from the extracellular domain of DR5 protein was produced with a peptide synthesizer. After control assays and confirmation of the correct amino acid sequence, it was injected to hens immunized to achieve high affinity IgYs. At the next step, the produced IgYs were extracted and examined for specificity against DR5 protein by ELISA assay. Subsequently, the anticancer effect of such IgYs was determined by MTT assay in the MCF7 human breast cancer cell line. The produced peptides successfully immunized hens and the produced antibodies which accumulated in egg yolk specifically recognized the DR5 protein. IgYs exerted significant toxicity and killed MCF7 cells as shown by MTT assay.

Prevalence of Cannabis Lifetime Use in Iranian High School and College Students: A Systematic Review, Meta-Analyses, and Meta-Regression.

Cannabis is the most widely used substance in the world. This study aimed to estimate the prevalence of cannabis lifetime use (CLU) in high school and college students of Iran and also to determine factors related to changes in prevalence. A systematic review of literature on cannabis use in Iran was conducted according to MOOSE guideline. Domestic scientific databases, PubMed/Medline, ISI Web of Knowledge, and Google Scholar, relevant reference lists, and relevant journals were searched up to April, 2014. Prevalences were calculated using the variance stabilizing double arcsine transformation and confidence intervals (CIs) estimated using the Wilson method. Heterogeneity was assessed by Cochran's Q statistic and I(2) index and causes of heterogeneity were evaluated using meta-regression model. In electronic database search, 4,000 citations were retrieved, producing a total of 33 studies. CLU was reported with a random effects pooled prevalence of 4.0% (95% CI = 3.0% to 5.0%). In subgroups of high school and college students, prevalences were 5.0% (95% CI = 3.0% to -7.0%) and 2.0% (95% CI = 2.0% to -3.0%), respectively. Meta-regression model indicated that prevalence is higher in college students (ß = 0.089, p < .001), male gender (ß = 0.017, p < .001), and is lower in studies with sampling versus census studies (ß = -0.096, p < .001). This study reported that prevalence of CLU in Iranian students are lower than industrialized countries. In addition, gender, level of education, and methods of sampling are highly associated with changes in the prevalence of CLU across provinces.