ali zekri

Breast cancer remained the leading cause of cancer-related death among women worldwide. Despite considerable advances in early detection and effective therapy, developing chemoresistance and metastatic spread to distant organs is still a pressing clinical challenge. The present study aims to investigate the role of Aurora-B as a potential oncogene in the progression of breast cancer.

Forty breast tumor samples and paired adjacent non-tumor tissues were collected. RNA was extracted and converted to cDNA according to manufacture protocols. The expression of Aurora-B was assessed using quantitative real-time PCR. The relationship between gene expression and the pathological features of the tumors, and the hormone receptors status of the patient’s tumors were also analyzed.

We found a significant overexpression of the Aurora-B gene in tumor samples compared to adjacent normal tissue (p value < 0.05). Moreover, the overexpression of Aurora-B was more increased in IDC tumors in compare to ILC breast tumors. There was not significant change between pre- and post-menopause periods.

Overexpression of oncogenic Aurora-B is associated with the progression of breast cancer. Aurora-B may represent an emerging therapeutic target in breast cancer treatment.

The novel coronavirus, known as a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a single-stranded RNA virus, from which structural and some accessory proteins are encoded. It seems that this newly emerged virus uses the ACE2 receptor to enter the cells in the human body. SARS-CoV-2 undergoes an intense immunological pressure in humans, and this generates mutations to bypass the immune system. Some mutations have been detected in this virus genome, which can induce changein viral potency. By performing pathway enrichment analysis over those genes and identifying relevant protein-protein interactions (PPIs), we were able to list essential pathways affected in infected cells. In this review, we mainly discuss genetic, intracellular mechanisms also diagnosis and feasible therapeutic targets of this novel coronavirus.

Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14. Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations.

Exons 1 and 6-7 of KRT 5 and exons 1 and 4-7 of KRT 14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools.

Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype [G96D (p.Gly96Asp) and F97I (p.Phe97Ile) in KRT5]. One of them showed a Dowling–Meara phenotype [A417P (p.Ala417Pro) and E477D (p.Glu477Asp) in KRT5] and another had a Koebner type phenotype [R397I (p.Arg397Ile) and Q444* (p.Gln444Ter) in KRT5]. A novel variant [G92E (p.Gly92Glu) in KRT5] in a double heterozygous state with a challenging variant [A413T (p.Ala413Thr) in KRT14] identified in one patient with Koebner type phenotype. Also, a previously reported mutation [I377T (p.Ile377Thr) in KRT14 gene] identified in this study.

The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed.

Waardenburg syndrome (WS) is a neurocristopathy with an autosomal dominant mode of inheritance, and considerable clinical and genetic heterogeneity. WS type II is the most common type of WS in many populations presenting with sensorineural hearing impairment, heterochromia iridis, hypoplastic blue eye, and pigmentary abnormalities of the hair and skin. To date, mutations of MITF, SOX10, and SNAI2 have been implicated in the pathogenesis of WS2. Although different pathogenic mutations have been reported in many ethnic groups, the data on Iranian WS2 patients is insufficient. 31 WS2 patients, including 22 men and 9 women from 14 families were included. Waardenburg consortium guidelines were employed for WS2 diagnosis. WS2 patients underwent screening for MITF, SOX10, and SNAI2 mutations using direct sequencing and MLPA analysis. Clinical evaluation revealed prominent phenotypic variability in Iranian WS2 patients. Sensorineural hearing impairment and heterochromia iridis were the most common features (67% and 45%, respectively), whereas anosmia was the least frequent phenotype. Molecular analysis revealed a de novo heterozygous c.640C>T (p.R214X) in MITF and a de novo heterozygous SOX10 gross deletion in the study population. Our data help illuminate the phenotypic and genotypic spectrum of WS2 in an Iranian series of patients, and could have implications for the genetic counseling of WS in Iran.

Colorectal cancer (CRC) is the third most prevalent cancer in the world with high rates of mortality, which makes it of great importance to be efficiently cured. Aurora kinase family (including Aurora A, B, and C) regulate several phases of cell cycle in mammalian cells. Aurora-B is overexpressed in various types of solid tumors and leukemia, and in that case, the prognosis is poor. AZD1152 is a selective inhibitor for Aurora kinase B. The purpose of this study is to investigate the effects of AZD1152 and its mechanism of action on two CRC cell lines. In this experimental study, two cell lines including Caco-2 and HCT-116, were used as models of CRC. Trypsin was utilized for passaging the mentioned cell lines. AZD1152 was provided with primary concentration of 1000 μM and diluted to achieve specific concentrations. Antitumor properties of AZD1152 on cell lines were investigated using MTT (Microculture Tetrazolium Test) and clonogenic assays. Student's t-test was also done to perform statistical analyses. The results of MTT assay indicated that 50 nM and 500 nM of AZD1152 effectively decreased metabolic activity in HCT-116 and Caco-2 cell lines by 25% and 50%, respectively. Also the mentioned drug inhibited clonogenic activity in the given cell lines. Altogether, this study suggests AZD1152 as a novel potential chemotherapeutic agent for treatment of CRC. However, more investigations are needed to uncover action mechanisms of AZD1152 in CRC treatment.

Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. Since human cytomegalovirus (HCMV) is frequently presented in the gingival sulcus fluid, we hypothesized that this virus would be important in the pathogenesis of oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the presence of active HCMV in different histopathological grades of OSCC in southeast of Iran. Forty eight individual specimens were evaluated in this study. Serial sections were obtained from paraffin-embedded tissue samples of OSCC biopsies. The frequency of HCMV was investigated using the real-time polymerase change reaction method after DNA extraction from biopsies. The mean age of the patients (66.7% female and 33.3% male) was 58.6 years. Only three cases (6.3%) of the grade I, OSCC biopsies, were positive for active HCMV with average load of 57.7 × 103. According to the low prevalence of HCMV in OSCC, it seems that this virus plays a minor role in this kind of cancer at least in southeast of Iran. More comprehensive studies are needed to investigate the oncomodulatory effect of this virus on OSCC.

Genetic instability is an important issue in cancer and including two important types of chromosome instability and microsatellite instability. Centrosome abnormality is a leading cause of chromosome instability. Centrosome plays as a microtubule organizing center (MTOC) to determine number، polarity and organization of interphase and metaphase microtubule. Centrosomes take part in cytoplasm organization، cell polarity and chromosome distribution to daughter cells. Numbers and function of centrosomes are regulated by genetic factors and polar mitotic apparatus. Cancer cells display a wide range of centrosome abnormality in in vitro and in vivo. Together، in this article we review recent and basic concepts of centrosome abnormality in cancer cells.

Silibinin is a traditionally well-known drug for its hepatoprotective efficacy against various types of liver afflictions. In addition, it has recently been considered broadly as a potential chemopreventive agent against many types of cancers. The current study was designed to evaluate the restrictive effects of pharmacological doses of silibinin on SKBR3, an ErbB2-overexpressed and ER-negative human breast carcinoma cell line. Effect of silibinin on metabolic activity and proliferation of human breast carcinoma (SKBR3) cell line were evaluated by MTT and BrdU assays respectively. Furthermore, the proapoptotic effect of silibinin was investigated using flow cytometry. The NF-κB phosphorylation assay was also used to assess the effect of silibinin on NF-κB activation. The alkalizing effect of silibinin on SKBR3 cell line was evaluated by measuring pH of media of the silibinin-treated cells compared to control. Our results indicate that silibinin inhibited metabolic activity and cell proliferation of SKBR3 cells in a dose-dependent manner. Moreover, silibinin significantly induced apoptosis in SKBR3 cells. On the other hand, silibinin significantly inhibited activation of NF-κB which is known to be highly active in this cell line. Alkalizing effect of silibinin was also observed. The results obtained here indicate that silibinin may be an efficacious therapeutic agent against ER-negative breast carcinomas with high inhibitory effect on NF-κB.

The study of specific genes expressed in the testis is important to understanding testis development and function. Spermatogenesis is an attractive model for the study of gene expression during germ cell differentiation. Spermatogenesis associated-19 (Spata-19) is a recently-identified important spermatogenesis-related gene specifically expressed in testis. Its protein product is involved in sperm cell development and reproduction. In this report we examined the expression of Spata-19 mRNA in mouse testis, fetus, and cell lines. Reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze Spata-19 mRNA expression in different stages of mouse testis development, mouse fetus, mouse embryonic fibroblasts (MEF), mouse embryonic stem cells (mESC), Sertoli cells, and NIH/3T3 cells. We identified a novel splice variant of Spata-19 in the mouse genome that it is expressed in the fetus and after the meiotic phase of spermatogenesis, and over-expressed in the post-meiotic stage of mouse spermatogenesis. This novel splice variant was absent in five days old mice testis, mESC, MEF, Sertoli, and NIH/3T3 cell lines. The Spata-19 has a large novel splice variant in mouse testis that is expressed beyond meiotic phase of testis development. We suggest that this new Spata-19 mRNA variant might be involved in mitochondrial maintenance in sperm cells, and might be correlated with androgen secretion and male fertility.

A goal of modern cancer research is to reach targeted therapies with drugs having fewer side effects. AZD1152 is a highly specific inhibitor of Aurora Kinase B، which leads to the programmed cell death by different mechanisms. The aim of this study was to evaluate the effects of AZD1152 on viability and metabolic activity of NB4 cells (APL derived cell line). The cells were treated with various concentrations of AZD1152. After 24، 48 and 72h treatments، the metabolic activity and viability of inhibitor-treated NB4 cells were assessed using MTT and trypan blue dye exclusion assays، respectively. Data were analyzed by applying student’s t-test (Microsoft Excel). A t 25، 50 and 100 nM، AZD1152 reduced the metabolic activity by 9. 2، 15. 5 and 56. 2% (after 24h)، 10. 3، 19. 5 and 59. 9% (after 48h)، and 17. 1، 28. 4 and 64. 8% (after 72h)، respectively. Meanwhile، the percentage of viability was decreased to about 51، 45 and 40% (after 24h)، 39، 36 and 30% (after 48h)، and 34، 32 and 28% (after 72h)، respectively. According to the results، AZD1152 has substantial efficacy on APL cell line and may be applied in some cases، e. g.، for patients who have relapse or who become refractory to the conventional chemotherapy. Further studies are needed to show the molecular mechanisms regulating effects of this anti-cancer agent.

The Cell cycle of eukaryotes is an ordered set of events, culminating in cell growth and division into two daughter cells. Cell cycle consists of G1, S, G2 and M phases. M phase is divided to five sub-phases of prophase, prometaphase, metaphase, anaphase and telophase. At the end, two daughter cells are separated by cytokinesis. Cell cycle has checkpoints that ensure passage through different steps. Mutation or over- expression into genes coding checkpoint proteins can cause cancer. Regulation of mitosis process is controlled by post translation in some protein kinases. CyclinB/Cdk1 initiates and makes progress mitosis. Some kinases, like Aurora kinases, NIMA and PLK, have vital role in mitosis. Aurora kinases have important roles in cell cycle, such as mitotic spindle assembly and metaphase chromosome bi-orientation. Aberrant expression of Aurora kinases can disrupt checkpoints and cause genomic instability to promote tumor initiation. Aurora kinase come in focus when they known as “Bona fida oncogens”. Human genome has three Aurora kinases, including Aurora kinases A, B, and C. Proteins with selective functions in cell cycle, especially cell cycle dependent kinases, are known as new drug targets for cancer treatment. Several studies have shown association of aurora kinases and malignancy; so, they have been considered as a target for developing new drugs in the treatment of cancer. Increasing our knowledge about function and regulation of these magic kinases can lead us to develop drugs for cancer treatment