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- Klinik und Poliklinik für Chirurgie Abt. für Unfall- und Wiederherstellungschirurgie (6) (remove)
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Chondrosarcoma is the second most common malign bone tumor in adults. Surgical
resection of the tumor is recommended because of its resistance to clinical treatment such as
chemotherapy and radiation therapy. Thus, the prognosis for patients mainly depends on sufficient
surgical resection. Due to this, research on alternative therapies is needed. Cold atmospheric plasma
(CAP) is an ionized gas that contains various reactive species. Previous studies have shown an
anti-oncogenic potential of CAP on different cancer cell types. The current study examined the effects
of treatment with CAP on two chondrosarcoma cell lines (CAL-78, SW1353). Through proliferation
assay, the cell growth after CAP-treatment was determined. A strong antiproliferative effect for
both cell lines was detected. By fluorescein diacetate (FDA) assay and ATP release assay, alterations
in the cell membrane and associated translocation of low molecular weight particles through the
cytoplasmic membrane were observed. In supernatant, the non-membrane-permeable FDA and
endogenously synthesized ATP detected suggest an increased membrane permeability after CAP
treatment. Similar results were shown by the dextran-uptake assay. Furthermore, fluorescence
microscopic G-/F-actin assay was performed. G- and F-actin were selectively dyed, and the ratio
was measured. The presented results indicate CAP-induced changes in cell membrane function and
possible alterations in actin-cytoskeleton, which may contribute to the antiproliferative effects of CAP.
Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology.
Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the
destruction of cell membrane integrity, have been investigated in many different types of tumors.
In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment
of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy
and the patient’s further prognosis. Whether the CAP influences this process is unknown, and the
first indications in this regard are addressed in this study. Methods: Two different devices, kINPen
and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly
and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes,
caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism
was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was
performed to examine the capillary tube formation abilities of HDMEC and their migration was
messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment,
a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was
performed. Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting
effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism
in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application.
These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay
showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results
were independent of the CAP device. Both the migration and tube formation of HDMEC were
significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP
treatment on a non-malignant cell line.
(1) Background: Chondrosarcoma (CS) is a malignant primary bone tumor with a cartilaginous origin. Its slow cell division and severely restricted vascularization are responsible for its poor responsiveness to chemotherapy and radiotherapy. The decisive factor for the prognosis of CS patients is the only adequate therapy—surgical resection. Cold atmospheric pressure plasma (CAP) is emerging as a new option in anti-cancer therapy. Its effect on chondrosarcomas has been poorly investigated. (2) Methods: Two CS cell lines—SW 1353 and CAL 78—were used. Various assays, such as cell growth kinetics, glucose uptake, and metabolic activity assay, along with two different apoptosis assays were performed after CAP treatment. A radius cell migration assay was used to examine cell motility. (3) Results: Both cell lines showed different growth behavior, which was taken into account when using the assays. After CAP treatment, a reduction in metabolic activity was observed in both cell lines. The immediate effect of CAP showed a reduction in cell numbers and in influence on this cell line’s growth rate. The measurement of the glucose concentration in the cell culture medium showed an increase after CAP treatment. Live-dead cell imaging shows an increase in the proportion of dead cells over the incubation time for both cell lines. There was a significant increase in apoptotic signals after 48 h and 72 h for both cell lines in both assays. The migration assay showed that CAP treatment inhibited the motility of chondrosarcoma cells. The effects in all experiments were related to the duration of CAP exposure. (4) Conclusions: The CAP treatment of CS cells inhibits their growth, motility, and metabolism by initiating apoptotic processes.
Non-invasive physical plasma (NIPP) achieves biomedical effects primarily through the formation of reactive oxygen and nitrogen species. In clinical use, these species interact with cells of the treated tissue, affecting the cytoplasmic membrane first. The present study investigated the permeability of the cytoplasmic membrane of breast cancer cells with different fluorescent dyes after NIPP treatment and determined the subsequent effects on cell viability. After NIPP treatment and the associated formation of reactive oxygen species, low molecular weight compounds were able to pass through the cytoplasmic membrane in both directions to a higher extent. Consequently, a loss of cellular ATP into the extracellular space was induced. Due to these limitations in cell physiology, apoptosis was induced in the cancer cells and the entire cell population exhibited decreased cell growth. It can be concluded that NIPP treatment disturbs the biochemical functionality of the cytoplasmic membrane of cancer cells, which massively impairs their viability. This observation opens a vast application horizon of NIPP therapy to treat precancerous and malignant diseases beyond breast cancer therapy.
Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors.Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve theclinical outcome for patients. However, they are accompanied by acute and chronic side effectsthat affect the quality of life of patients, motivating novel research lines on therapeutic optionsfor the treatment of sarcomas. Previous experimental work with physical plasma operated atbody temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on differentcancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcomaentities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS,MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lineswas observed. CAP-induced alterations in cell membrane functionality were detected by performinga fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications ofthe cell membrane and modifications in the actin cytoskeleton composition were examined usingfluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore,the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays.The observations suggest that a single CAP treatment of bone sarcoma cells may have significantanti-oncogenic effects and thus may be a promising extension to existing applications.
Introduction
Although shoulder girdle injuries are frequent, those of the medial part are widely unexplored.
Our aim is to improve the knowledge of this rare injury and its management in Germany
by big data analysis.
Methods
The data are based on ICD-10 codes of all German hospitals as provided by the German
Federal Statistical Office. Based on the ICD-10 codes S42.01 (medial clavicle fracture,
MCF) and S43.2 (sternoclavicular joint dislocation, SCJD), anonymized patient data from
2012 to 2014 were evaluated retrospectively for epidemiologic issues. We analyzed especially
the concomitant injuries and therapy strategies.
Results
A total of 114,003 cases with a clavicle involving shoulder girdle injury were identified with
12.5% of medial clavicle injuries (MCI). These were accompanied by concomitant injuries,
most of which were thoracic and craniocerebral injuries as well as injuries at the shoulder/
upper arm. A significant difference between MCF and SCJD concerning concomitant injuries
only appears for head injuries (p = 0.003). If MCI is the main diagnosis, soft tissue injuries
typically occur as secondary diagnoses. The MCI are significantly more often
associated with concomitant injuries (p < 0.001) for almost each anatomic region compared
with lateral clavicle injuries (LCI). The main differences were found for thoracic and upper
extremity injuries. Different treatment strategies were used, most frequently plate osteosynthesis
in more than 50% of MCF cases. Surgery on SCJD was performed with K-wires,
tension flange or absorbable materials, fewer by plate osteosynthesis.
Conclusions
We proved that MCI are rare injuries, which might be why they are treated by inhomogeneous
treatment strategies. No standard procedure has yet been established. MCI can
occur in cases of severely injured patients, often associated with severe thoracic or other
concomitant injuries. Therefore, MCI appear to be more complex than LCI. Further studies
are required regarding the development of standard treatment strategy and representative
clinical studies.