Negative impact of wound complications on oncologic outcome of soft tissue sarcomas of the chest wall

A link of complications with worse oncologic prognosis has been established for multiple malignancies, while the limited literature on soft-tissue sarcomas is inconclusive. The aim of this study was to examine risk factors and the oncologic impact of wound complications after curative resection of primary soft-tissue sarcomas of the chest wall. Patients with primary soft tissue sarcomas of the chest wall were identified. Groups with and without wound complications were compared by using univariate and multivariate analysis to identify risk factors. For patients with clear surgical margins (R0), univariate and multivariate analysis of factors associated with 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), and disease specific survival (DSS) were performed. A total of 102 patients were included in the study. Wound complications occurred in 11 patients (10.8%) within 90 days. Cardiovascular morbidity and operation time represented independent risk factors for wound complications. In 94 patients with clear surgical margins, those with wound complications had an estimated 5-year LRFS of 30% versus 72.6% and a 5-year DSS of 58.3% versus 82.1%. Wound complications could be identified as an independent predictor for worse LRFS and DSS. Patients with a high risk of wound complications should be identified and strategies implemented to reduce surgical complications and possibly improve oncologic prognosis

Alterations in pectoralis muscle cell characteristics after radiation of the human breast insitu\textit in situ

The life-time risk of being diagnosed with breast cancer is ~12%, hence breast cancer is by far the most common cancer among women. The multimodal treatment concept of breast cancer often intends radiation. The utilized ionizing radiation leads changes in the tissue resulting in tissue damage due to an alteration of molecular factors. The goal of this study was to identify the role of muscle-catabolic proteins after radiation of human pectoralis major muscles in situ. Tissue of the pectoralis major muscle was collected in 12 breast cancer patients after radiation (maximum 3 years after radiation) undergoing a deep inferior epigastric perforator free-flap breast reconstruction. At the same time, an intraindividual comparison to rectus abdominis muscle was carried out upon free-flap elevation. Immunological properties, cell proliferation, differentiation as well as the expression profile of the muscle tissue were investigated through immunohistological reactions, a DNA-microarray and histology. We found significantly increased neutrophil immigration in the radiated muscle tissue. At the same time, proteins responsible for muscular atrophy and apoptosis were significantly elevated in immunohistochemistry. A DNA microarray detected immunological upregulation and myo-differentiative disorders in radiated muscle tissue. This novel study investigating catabolism in radiated muscle in situ can serve as a basis for the treatment of radiation-accompanied muscle disorders

Myostatin deficiency protects C2C12 cells from oxidative stress by inhibiting intrinsic activation of apoptosis

Ischemia reperfusion (IR) injury remains an important topic in clinical medicine. While a multitude of prophylactic and therapeutic strategies have been proposed, recent studies have illuminated protective effects of myostatin inhibition. This study aims to elaborate on the intracellular pathways involved in myostatin signaling and to explore key proteins that convey protective effects in IR injury. We used CRISPR/Cas9 gene editing to introduce a myostatin $\textit {(Mstn)}$ deletion into a C2C12 cell line. In subsequent experiments, we evaluated overall cell death, activation of apoptotic pathways, ROS generation, lipid peroxidation, intracellular signaling via mitogen-activated protein kinases (MAPKs), cell migration, and cell proliferation under hypoxic conditions followed by reoxygenation to simulate an IR situation in vitro (hypoxia reoxygenation). It was found that mitogen-activated protein kinase kinase 3/6, also known as MAPK/ERK Kinase 3/6 (MEK3/6), and subsequent p38 MAPK activation were blunted in C2C12-$it Mstn^{−/−}$ cells in response to hypoxia reoxygenation (HR). Similarly, c-Jun N-terminal kinase (JNK) activation was negated. We also found the intrinsic activation of apoptosis to be more important in comparison with the extrinsic activation. Additionally, intercepting myostatin signaling mitigated apoptosis activation. Ultimately, this research validated protective effects of myostatin inhibition in HR and identified potential mediators worth further investigation. Intercepting myostatin signaling did not inhibit ROS generation overall but mitigated cellular injury. In particular, intrinsic activation of apoptosis origination from mitochondria was alleviated. This was presumably mediated by decreased activation of p38 caused by the diminished kinase activity increase of MEK3/6. Overall, this work provides important insights into HR signaling in C2C12-$it Mstn^{−/−}$ cells and could serve as basis for further research