A mini‐F region 800 bp long, located between the two F origin sites, plays an essential role in the relationship between the F plasmid and its host. This region comprises two sets of overlapping coding sequences: the first set codes for the newly identified H1 and H2 polypeptides; the second set codes for polypeptides G1 and G2. A mini‐F amber mutation (Ham22) causes the virtual disappearance of polypeptides H1 and H2 but only slightly reduces synthesis of polypeptides G1 and G2. This mutation: (i) renders mini‐F hybrids lethal to the host cells (conditional Hos‐ phenotype for host survival) and (ii) causes the induction of a resident prophage in recA+ strains (conditional Map‐ phenotype for maintenance of the prophage). When an additional mutation prevents the synthesis of polypeptides G1 and G2, both the lethal character and the induction of the prophage are abolished. We conclude: (i) that polypeptides G1 and/or G2 are specific mini‐F polypeptides involved in the plasmid‐mediated killing effect and in the recA‐dependent induction of the resident prophage and (ii) that, in normal conditions, polypeptides H1 and/or H2 negatively control (directly or indirectly) the action of polypeptides G1 and/or G2. In relation to the analysis of indirect induction mediated by u.v.‐irradiated lambda mini‐F hybrids, we propose that polypeptides G1 and/or G2 are specific mini‐F products involved in the activation of the bacterial SOS pathway. The H1/H2 and G1/G2 polypeptides could constitute the controlled mini‐F signal enabling the coordination between cell division and F plasmid replication.
4110 Background: Neoadjuvant chemotherapy in a perioperative setting has proven valuable in locally advanced resectable colon cancer (CC) in terms of toxicity, postoperative morbidity and downstaging, but its effect on oncological outcomes remains uncertain. Methods: Prodige 22 was a randomized multicenter phase II trial in patients with resectable high-risk T3, T4 and/or N2 CC on baseline CT-scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type (wt) patients a third arm testing perioperative FOLFOX-cetuximab was added. Primary endpoint was the Tumor Regression Grade. Secondary endpoints were 3-years overall (OS), disease-free survival (DFS) and time to recurrence (TTR). Results: 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped for futility. The remaining 104 patients (control, n = 52; FOLFOX peri-op n = 52) represented our intention-to-treat population. In the FOLFOX peri-op group, 96% received the schedule 4 cycles prior to surgery and all but one underwent adjuvant FOLFOX for a total of 12 cycles. In the control arm, 38 patients received adjuvant FOLFOX (1 postoperative death and 13 low-risk stage II patients). Median follow-up was 54.3 months [48.5-57.2]. Nineteen deaths and 26 disease recurrences were observed leading to a 3 years-OS of 90.3% in both arms (p = 0.7) and to a 3-years DFS of 76.8% and 69.2% in the peri-op and control arm respectively (p = 0.6). A trend to a better TTR in the peri-op arm was observed with a 3-years TTR of 82% as compared to 72% in the control arm (p = 0.3). No benefit from adding Cetuximab was observed in the 16 RAS-wt treated patients. Conclusions: In this pilot randomized study, perioperative FOLFOX chemotherapy has no detrimental effect on long term oncological outcomes and may be an option for some patients with locally advanced CC. A pooled analysis of randomized trials testing peri-operative strategies in this setting is warranted. Clinical trial information: NCT01675999 .
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