GSK3β is a multifunctional serine/threonine kinase that regulates various cellular pathways, depending on its substrates for phosphorylation. It is evident that regulation of Wnt/β-catenin signaling is only one of its diverse functions. Since oncogenic transcription factors (e.g., c-Jun, c-Myc) and proto-oncoproteins (i.e., β-catenin, Gli proteins) are putative GSK3β substrates for phosphorylation-dependent inactivation, it is hypothesized that GSK3β interferes with cellular neoplastic transformation and tumor development, as exemplified by its activity in Wnt/β-catenin signaling. However, only a few studies have addressed its role(s) in human cancer, and these studies have reported differing effects of GSK3β on cancer cells. Using GSK3β deficient mouse embryonic fibroblasts, it was shown that GSK3β plays a crucial role in cell survival mediated by the nuclear factor-kappaB (NF-κB) pathway (Nature 2000; 406:86-90). Interestingly, we have recently shown that the Wnt/β-catenin and NF-κB pathways were co-activated in colorectal cancer by dysregulation in the ubiquitin system (J Natl Cancer Inst 2004; 96:1161-70). Thus, these observations bring forward apparently opposing notions regarding the functions of GSK3β in neoplastic cells on the one hand, removing a neoplastic trigger by phosphorylation-dependent degradation of β-catenin oncoprotein in the ubiquitin system, and on the other, contributing to a cell proliferation and survival pathways by regulating NF-κB. The present study was therefore undertaken to clarify the role of GSK3β in cancer by analyzing expression and activity of this kinase in colon cancer cells and clinical colorectal cancers and by investigating its effects on cancer cells. In colon cancer cell lines and colorectal cancer patients, levels of GSK3β expression and its active form were higher in tumor cells than in their normal counterparts; these findings were independent of nuclear accumulation of β-catenin oncoprotein in the tumor cells. Inhibition of GSK3β activity by its Ser9 phosphorylation was defective in colorectal cancers but preserved in non-neoplastic cells and tissues. Strikingly, inhibition of GSK3β activity by chemical inhibitors and its expression by RNA interference targeting GSK3β induced apoptosis and attenuated proliferation of colon cancer cells in vitro. Our findings demonstrate an unrecognized role of GSK3β in tumor cell survival and proliferation and warrant proposing this kinase as a novel and potential therapeutic target in colorectal cancer.

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Oxacillin resistance was present in 99 of 277 (36%) consecutive Staphylococcus aureus isolates collected from hospital patients in Tehran during a 15-month period (January 2004-March 2005). The majority of isolates (77/99 = 78%) had been cultured from wounds or blood. The staphylococcal cassette chromosome mec (SCCmec) types and antimicrobial susceptibility patterns of 99 methicillin-resistant S. aureus (MRSA) strains were determined. Disk diffusion and agar dilution methods were used to determine the susceptibility of isolates to antimicrobial agents as instructed by Clinical and Laboratory Standards Institute. The presence of mecA and SCCmec types was determined by PCR and multiplex PCR. All MRSA isolates were susceptible to vancomycin (MIC90

Cervical cancer is a human papilloma virus (HPV)-related cancer, but most HPV infections are transient or intermittent and resolve spontaneously. Thus, other factors, such as cervical microflora, which are dominated by lactobacilli, must be involved in invasive cervical carcinoma development after HPV infection. Previous studies have demonstrated that lactobacilli have antitumour effects, and it is possible that vaginal lactobacilli prevent cervical cancer. Here we examined the proliferative and apoptotic responses of normal and tumour cervical cells to common vaginal lactobacilli components by investigating human normal fibroblast-like cervical (normal cervical) and HeLa (cervical tumour) cell responses to Lactobacillus gasseri and Lactobacillus crispatus. The effects of different lactobacilli components, such as culture supernatants, cytoplasmic extracts, cell-wall extracts and live cells, were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, trypan blue staining, lactate dehydrogenase assay and colorimetric caspase-3 activity assay. Changes in caspase-3 and human chorionic gonadotropin b (hCGb) expression were analysed by quantitative RT-PCR. Tumour cell growth inhibition by culture supernatants was higher than that by pH-and lactateadjusted controls. However, the effects of the supernatants on normal cells were similar to those of lactate-adjusted controls. Apoptosis was inhibited by supernatants, which was consistent with higher hCGb expression since hCG inhibits apoptosis. Our study demonstrated that common vaginal lactobacilli exert cytotoxic effects on cervical tumour cells, but not on normal cells, and that this cytotoxicity is independent of pH and lactate. Our results encourage further studies on the interaction between lactobacilli and cervical cells, and administration of common vaginal lactobacilli as probiotics.

We investigated polymorphisms of plasminogen activator inhibitor-1 (PAI-1), angiotensin converting enzyme (ACE ) and coagulation factor XIII (FXIII) genes and their association with recurrent spontaneous abortion (RSA) in Iranian patients and normal healthy controls. Ten (18.5%) patients were homozygote (4G/4G) for PAI-1 polymorphism, in contrast with two (2%) controls (p = 0.001). Patients with homozygote 4G mutation were significantly more prone to RSA in contrast to others (odds ratio: 11.0, 95% CI: 2.3-52.4). Nineteen (30.2%) patients and 25 (26.6%) controls were homozygote (DD) for ACE polymorphism. We observed only two patients and one control with homozygosity (34leu) for FXIII polymorphism. 4G/4G polymorphism for PAI-1 gene could be a thrombophilic mutation leading to abortion in Iranian population.