Identification of novel hypoxia response genes in human glioma cell line a172.

OBJECTIVE(S): Hypoxia is a serious challenge for treatment of solid tumors. This condition has been manifested to exert significant therapeutic effects on glioblastoma multiform or (WHO) astrocytoma grade IV. Hypoxia contributes numerous changes in cellular mechanisms such as angiogenesis, metastasis and apoptosis evasion. Furthermore, in molecular level, hypoxia can cause induction of DNA breaks in tumor cells. Identification of mechanisms responsible for these effects can lead to designing more efficient therapeutic strategies against tumor progression which results in improvement of patient prognosis. Materials and Methods : In order to identify more hypoxia regulated genes which may have a role in glioblastoma progression, cDNA-AFLP was optimized as a Differential display method which is able to identify and isolate transcripts with no prior sequence knowledge. RESULTS: Using this method, the current study identified 120 Transcription Derived Fragments (TDFs) which were completely differentially regulated in response to hypoxia. By sequence homology searching, the current study could detect 22 completely differentially regulated known genes and two unknown sequence matching with two chromosome contig and four sequence matches with some Expressed Sequence Tags (ESTs). CONCLUSION: Further characterizing of these genes may help to achieve better understanding of hypoxia mediated phenotype change in tumor cells.

Identification of Xq22.1-23 as a region linked with hereditary recurrent spontaneous abortion in a family.

BACKGROUND: Recurrent spontaneous abortion (RSA) is one of the most common health complications with a strong genetic component. Several genetic disorders were identified as etiological factors of hereditary X linked RSA. However, more genetic factors remain to be identified. OBJECTIVE: In this study we performed linkage analysis on a large X linked RSA pedigree to find a novel susceptibility locus for RSA. MATERIALS AND METHODS: A linkage scan using 11 microsatellites was performed in 27 members of a large pedigree of hereditary X-linked RSA. Two point parametric Linkage was performed using Superlink v 1.6 program. RESULTS: Evidence of linkage was observed to markers at Xq23, DXS7133 and at Xq22.1 DXS101, with LOD score of 3.12 and 1.60, respectively. CONCLUSION: Identified locus in this study may carry a responsible gene in RSA. Narrowing down of this region may leads to identification of this gene. This article extracted from M.Sc. thesis. (Sahar Shekouhi).

The role of tumor protein 53 mutations in common human cancers and targeting the murine double minute 2-p53 interaction for cancer therapy.

The gene TP53 (also known as protein 53 or tumor protein 53), encoding transcription factor P53, is mutated or deleted in half of human cancers, demonstrating the crucial role of P53 in tumor suppression. There are reports of nearly 250 independent germ line TP53 mutations in over 100 publications. The P53 protein has the structure of a transcription factor and, is made up of several domains. The main function of P53 is to organize cell defense against cancerous transformation. P53 is a potent transcription factor that is activated in response to diverse stresses, leading to the induction of cell cycle arrest, apoptosis or senescence. The P53 tumor suppressor is negatively regulated in cells by the murine double minute 2 (MDM2) protein. Murine double minute 2 favors its nuclear export, and stimulates its degradation. Inhibitors of the P53-MDM2 interaction might be attractive new anticancer agents that could be used to activate wild-type P53 in tumors. Down regulation of MDM2 using an small interfering RNA (siRNA) approach has recently provided evidence for a new role of MDM2 in the P53 response, by modulating the inhibition of the cyclindependent kinase 2 (cdk2) by P21/WAF1 (also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1).

Cleft Palate induced by Sulfur Mustard in mice fetus.

Sulfur Mustard (SM) is a chemical warfare agent which was widely used in the World War I and more recently during Gulf war in the early 1980s'. SM is a strong alkylating agent with known mutagenic and carcinogenic effects; but only few studies have been published on its teratogenicity. Since SM has been widely used as a chemical weapon by the Iraqi regime against the Iranian soldiers as well as the civilian population particularly pregnant women in the border area; therefore, the investigation of SM adverse effects on cleft malformations which is one of the most frequent congenital anomalies is considered in this study. An experimental work has been carried out in embryopathy in mouse with intraperitoneal injection of 0.75 and 1.5 mg/kg SM at different periods of gestation. Cleft lip and palate were examined by stereomicroscopy. Current data demonstrate that exposure with SM on the 11th day of gestation can increase the incidence of cleft defects in comparison with control group (P<0.001). These results also show that SM treatment in GD 11 and 13 can lead to more anomalies compared with GD 14 (P<0.001). They also show that the teratogenic effects of SM are restrictively under the influence of the threshold dose and time of gestation. The present results suggest that exposure to sufficient doses of SM on critical days of gestation may increase the risk of congenital cleft malformations.

The Incidence of Spontaneous Abortion in Mothers with Blood Group O Compared with other Blood Types.

Although ABO incompatibility between mother and fetus has long been suspected as cause of spontaneous abortion in man, its precise contribution has not been completely resolved. In spite of reports in which the incompatible mating was recognized to be a cause of habitual abortion, and which eventually results in infertility or a reduction in the number of living children compared with the number in compatible matings, such effects were not observed in other studies. The aim of this review article was to show some evidence of relationship between ABO incompatibility and spontaneous abortion.