Survival and risk of breast cancer recurrence after breast reconstruction with deep inferior epigastric perforator flap.

BACKGROUND: Women who undergo autologous breast reconstruction have been reported to have an increased risk of breast cancer recurrence compared with those who have mastectomy alone. It has been suggested that more extensive surgery possibly activates dormant micrometastases. The aim of this study was to evaluate whether delayed unilateral deep inferior epigastric perforator (DIEP) flap reconstruction after mastectomy increases the risk of breast cancer recurrence or affects mortality among women previously treated for breast cancer. METHODS: This was a matched retrospective cohort study including women with a previous unilateral invasive breast cancer who received a delayed DIEP flap breast reconstruction and a control cohort of individually matched women with unilateral breast cancer who underwent mastectomy but no autologous breast reconstruction. Matching criteria comprised: year of diagnosis (+/-3 years), age at diagnosis (+/-5 years), type of cancer and demographic region. The primary endpoints were local recurrence or distant metastasis, and overall mortality was a secondary endpoint. Absolute risk of recurrent disease and mortality was analysed, and relative risks were estimated using Cox proportional hazards analysis. RESULTS: There were 225 women in the DIEP cohort and 450 in the no-DIEP cohort. The median follow-up time was 125 months. There was no difference in absolute risk of recurrence between the cohorts. The hazard ratio for breast cancer recurrence in DIEP versus no-DIEP cohorts was 0·76 (95 per cent c.i. 0·47 to 1·21). CONCLUSION: There is no increased risk in breast cancer recurrence after delayed DIEP flap reconstruction compared with mastectomy alone.

In vivo expression and genomic organization of the mouse cyclin I gene (Ccni).

Cyclins control cell-cycle progression by regulating the activity of cyclin-dependent kinases. Cyclin I was recently added to the cyclin family of proteins because of the presence of a cyclin box motif in the deduced amino-acid sequence. Cyclin I may share functional roles with cyclin G1 and G2 because of the high structural similarity between their deduced amino-acid sequences. However, the biological and functional roles of this subclass of cyclins remain obscure. The mouse cyclin G1 and G2 genes have previously been cloned and characterized. In this report, we describe the cloning of the mouse homolog of cyclin I. The cyclin I cDNA sequence was used to determine the genomic organization of the mouse cyclin I gene which co-localizes with cyclin G2 to chromosome 5E3.3-F1.3. Cyclin I was transcribed from seven exons distributed over more than 19kb of genomic sequence. The expression of cyclin I was determined in various tissues, but no clear correlation with the proliferative state was found. Furthermore, in contrast to cyclin G1, cyclin I expression was stable during cell-cycle progression after partial hepatectomy in both the absence and presence of DNA damage. Transient expression of cyclin I-green fluorescent protein (GFP) fusion proteins in cell lines showed that cyclin I was distributed throughout the cell in contrast with the mainly cytoplasmic localization of cyclin G2 and nuclear localization of cyclin G1. Our results indicate that despite the close structural similarity between cyclin G1, G2 and I, these three proteins are likely to have distinct biological roles.

Gene structure and chromosomal localization of mouse cyclin G2 (Ccng2).

Cyclins are essential activators of cyclin-dependent kinases (Cdk) which, in turn, play pivotal roles in controlling transition through cell-cycle checkpoints. Cyclin G2 is a recently discovered second member of the G-type cyclins. The two members of the G-type cyclins, cyclin G1 and cyclin G2, share high structural similarity but their function remains to be defined. Here we characterize the structure of the mouse cyclin G2 gene by first cloning and sequencing the full-length mouse cyclin G2 cDNA. The cyclin G2 cDNA was used to isolate the cyclin G2 gene from a BAC library and to establish that the gene was transcribed from eight exons spanning a total of 8604bp. The cyclin G2 gene was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 5E3.3.-F1.3. This region is syntenic to a region on human chromosome 4. The expression of cyclins G1 and G2 was examined in various tissues, but no correlation between expression patterns of the two genes was observed. However, during hepatic ontogenesis the cyclin G2 expression level decreased with age, whereas cyclin G1 expression increased. Transient expression of cyclin G2-green fluorescent protein (GFP) fusion protein in NIH3T3 cells showed that cyclin G2 is essentially a cytoplasmic protein, in contrast to the largely nuclear localization of cyclin G1. Our data suggest that, despite the close structural similarity between mouse cyclins G1 and G2, these proteins most likely perform distinct functions.

Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model.

Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumors, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. The interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in a transgenic mouse model has been analyzed. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Furthermore, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice, whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine.