INTRODUCTION: Mesenchymal stem cells (MSCs) have been described in breast cancer models to migrate towards carcinoma and integrate into tumor associated stroma supporting tumor growth, increasing their metastatic potency and contributing to tumor-angiogenesis. Platelet-derived growth factor (PDGF) isoforms (AA, BB, CC) stimulate growth, survival and motility of MSCs and certain other cell types. Noteworthy, breast carcinomas are known to express PDGF. We aim to further shed light on i) the relevance of the different PDGF isoforms on adipose tissue derived stem cells (ASCs) migration and ii) the underlying pathway dependent on PDGF stimulation. MATERIALS AND METHODS: Breast cancer cell lines were purchased and ASC's were isolated from murine subcutaneous adipose tissue. The transmigration of ASC's towards the PDGF-isoforms was assessed by using recombinant human PDGF-AA, PDGF-BB and PDGF-CC in a trans-well culture dish system. Transmigrated ASC's were quantified in 5 randomly selected fields per condition using fluorescence microscopy after calcein-staining. PDGF-BB depended transmigration of ASC's was verified by downregulation and overexpression of PDGF-BB in breast cancer cell line using lentiviral vectors. In addition, a PI3-kinase inhibitor (LY294002) and a MAP-kinase inhibitor (PD98059) were used to identify the pathway involved in the PDGF-BB mediated migration of ASC's towards tumor. RESULTS: ASC's transmigration significantly increased towards PDGF AA at 50 ng and only showed further increase by 500 ng which was similar to cell behavior when exposed to PDGF CC. In comparison, PDGF-BB significantly increased ASC's transmigration already at a low level of 5 ng with further significant increase for 20 ng and 40 ng. Cell transmigration was blocked with PDGFR-␣ antibodies but only for PDGF-AA and PDGF-CC whereas PDGFR- blockage showed a significant effect on transmigration for PDGF-BB and PDGF-CC but not for PDGF-AA. Neutralizing antibodies in combination with PDGF receptor blockage confirmed findings. In addition, only PI3-kinase inhibitor but not the MEK-1 selective inhibitor caused a significant decrease of transmigration for ASCs towards breast cancer cells. DISCUSSION: The transmigration of ASC's is most significantly enhanced by PDGF-BB via the PI3-kinase pathway. This data support that PI3-kinase is an important key player for MSC migration towards malignancy which need further research to prevent tumor progression in early disease stage.
The results of this prospective interventional trial could not detect any negative impact of vasopressors, neither for the primary endpoint of flap survival nor for the overall patient outcome. The fear of vasopressor associated flap complications has led to a traditional liberal fluid administration, which failed to demonstrate any benefits when compared to a fluid restrictive vasopressor strategy.
Background
Breast reconstruction is an important coping tool for patients undergoing a mastectomy. There are numerous surgical techniques in breast reconstruction surgery (BRS). Regardless of the technique used, creating a symmetric outcome is crucial for patients and plastic surgeons. Three-dimensional surface imaging enables surgeons and patients to assess the outcome’s symmetry in BRS. To discriminate between autologous and alloplastic techniques, we analyzed both techniques using objective optical computerized symmetry analysis. Software was developed that enables clinicians to assess optical breast symmetry using three-dimensional surface imaging.
Methods
Twenty-seven patients who had undergone autologous (n = 12) or alloplastic (n = 15) BRS received three-dimensional surface imaging. Anthropomorphic data were collected digitally using semiautomatic measurements and automatic measurements. Automatic measurements were taken using the newly developed software. To quantify symmetry, a Symmetry Index is proposed.
Results
Statistical analysis revealed that there is no difference in the outcome symmetry between the two groups (t test for independent samples; p = 0.48, two-tailed).
Conclusion
This study’s findings provide a foundation for qualitative symmetry assessment in BRS using automatized digital anthropometry. In the present trial, no difference in the outcomes’ optical symmetry was detected between autologous and alloplastic approaches. Level of evidence Level IV.
Level of Evidence IV
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The skin sparing mastectomy combined with immediate reconstruction by DIEAP-flap provides an excellent therapeutic option for patients, who are suitable for this technique, which takes into account not only the form but also the sensitivity of the breast.
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