Bacteria have a great capacity for adjusting their metabolism in response to environmental changes by linking extracellular stimuli to the regulation of genes by transcription factors. By working in a co-operative manner, transcription factors provide a rapid response to external threats, allowing the bacteria to survive. This review will focus on transcription factors MarA, SoxS and Rob in Escherichia coli, three members of the AraC family of proteins. These homologous proteins exemplify the ability to respond to multiple threats such as oxidative stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides. MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more than 40 regulatory target genes. As their regulons overlap, a finely tuned adaptive response allows E. coli to survive in the presence of different assaults in a co-ordinated manner. These regulators are well conserved amongst Enterobacteriaceae and due to their broad involvement in bacterial adaptation in the host, have recently been explored as targets to develop new anti-virulence agents. The regulators are also being examined for their roles in novel technologies such as biofuel production.

The purpose of this study was to evaluate patient selection, local control, survival and late toxicity of posthysterectomy adjuvant radiotherapy and compare adjuvant external beam therapy and high-dose rate (HDR) brachytherapy versus HDR brachytherapy alone. A retrospective analysis was performed on a series of 225 patients with endometrial cancer treated with external beam radiotherapy and HDR brachytherapy or HDR brachytherapy alone posthysterectomy from 1985 to June 1993. Of these 225 patients, 82 received external beam radiotherapy and brachytherapy and 143 received brachytherapy alone. The HDR fraction size was 8.5 Gy prescribed to the mucosal surface; two fractions were given after external beam and four fractions if brachytherapy alone was used. The median follow-up was 6.9 years. The patients who received combined external beam and brachytherapy had higher stage and grade tumors. The survival outcome was similar for either group when matched for stage. Overall relapse-free survival at five years was 96% and 81%, respectively for brachytherapy alone and combined adjuvant therapy. Pelvic recurrence was seen in 2.7% of patients. Toxicity was more common with external beam radiotherapy and brachytherapy compared to brachytherapy alone (45.1% vs 23.1%, P = 0.003). However, moderate or severe toxicity was rare but again was more common in the combined radiotherapy group (8.5% vs 2.1%, P = 0.04). There was a non-significant trend to increased toxicity after lymphadenectomy and external beam radiotherapy compared with patients who did not have a staging lymphadenectomy prior to external beam radiotherapy (62% vs 38%, P = 0.16). Adjuvant radiotherapy can be individualized and be based upon the information provided by the pathological specimens, which excluded external beam radiotherapy if a lymphadenectomy was performed and there was no evidence of extra-uterine disease. This study found more toxicity associated with adjuvant radiotherapy compared with other studies, but this may reflect different reporting criteria. There was more toxicity related to external beam radiotherapy and brachytherapy compared to brachytherapy alone. The two HDR brachytherapy protocols used in this series appear effective and safe.

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