Free Flaps for Skin and Soft Tissue Reconstruction in the Elderly Patient: Indication or Contraindication.

BACKGROUND: Increased lifespan and the improvement of medical treatment have given rise to research in reconstructive procedures in elderly patients. Higher postoperative complication rates, longer rehabilitation, and surgical difficulties remain a problem in the elderly. We asked whether a free flap in elderly patients is an indication or a contraindication and performed a retrospective, monocentric study. METHODS: Patients were divided into two groups (YOUNG 0-59 years; OLD > 60 years). The endpoint was the survival of flaps and their dependence on patient- and surgery-specific parameters using multivariate analysis. RESULTS: A total of 110 patients (OLD n = 59) underwent 129 flaps. The chance of flap loss increased as soon as two flaps were performed in one surgery. Anterior lateral thigh flaps had the highest chance for flap survival. Compared with the lower extremity, the head/neck/trunk group had a significantly increased chance of flap loss. There was a significant increase in the odds of flap loss in linear relation to the administration of erythrocyte concentrates. CONCLUSION: The results confirm that free flap surgery can be indicated as a safe method for the elderly. Perioperative parameters such as two flaps in one surgery and transfusion regimens must be considered as risk factors for flap loss.

[Academic Careers in Medicine: a Sex-Related Analysis of Career Goals]. / Akademische Karriere in der Medizin: eine geschlechterbezogene Analyse zu beruflichen Zielen.

AIM OF THE STUDY: For female and male physicians of the clinical-academic mid-level staff, working conditions as well as the attitude towards profession and career play a decisive role. For years, there has been an increasing proportion of women in medicine. Despite this increase, a significant sex incongruence is still evident, especially in academic medicine. The aim of this work was to analyze current opinions of female and male physicians on sex-related aspects for career. METHODS: By means of an online survey, medical mid-level staff from university and peripheral hospitals were asked about professional biographical as well as career-related topics and the data analyzed in terms of the sexes. RESULTS: Compared to their male counterparts, female physicians had lower career goals and mainly aimed to qualify as senior physicians. Women planned to have families and raise children earlier in their careers. Men were more likely to have their professional careers in mind during the same time period. Although only just under 47% of respondents considered an academic career to be worthwhile, 65% continued to rate the acquisition of an academic title highly. When evaluating equal treatment by superiors, female physicians tended to feel disadvantaged in their professional careers compared to male physicians. Thus, physicians rated the treatment by their respective superiors as characterized by the quality of the work (44% for both genders of superiors) or dependent on sympathy (female superiors 30%; male superiors 24%). Female physicians, however, saw a preference for male colleagues in 37% of male superiors. CONCLUSION: Despite a significantly larger proportion of women in medicine for decades, there is still an incongruence in sexes in favor of men in management positions. The professional and private goals of women and men differ significantly depending on their age decade. The academic career per se is increasingly losing importance, although the acquisition of academic degrees still seems to be desirable. Therefore, to improve the future of academic medicine, significant structural changes are needed to enable projectable career paths (e. g., tenure track, assistant professorship, young medical professionals model) for mid-level academic staff.

[Balancing Family and Career in Medicine: Greatly Desired but Given Little Consideration Results of the Study Arm VI of the KARiMED Study]. / Vereinbarkeit von Familie und Beruf in der Medizin: vom großen Wunsch und wenig Berücksichtigung.

AIM OF THE STUDY: Family life and professional practice are both highly important for young physicians. Accordingly, a good balancing of both areas of life is necessary. Despite political framework conditions and legal requirements that have been in place for years, implementation of measures to achieve this seems to be difficult, especially in medicine, and is associated with great reservations and problems on the part of those involved. METHODS: By means of an online survey, the medical mid-level staff from university and peripheral hospitals was questioned on topics related to family, children and professional biographical as well as career-relevant topics and subsequently analyzed on a gender-specific basis. RESULTS: Of the study participants, 65.1% were married and already had children or expressed a desire to have children (86.0%). Most were employed full-time (80.8%). The majority of part-time employees were female (87.4%). For 34.6%, there was a career break of 18.5±21.3 months, 87.8% of which were taken due to pregnancy or children. Female physicians generally took significantly more parental leave than male physicians (6-12 months: females 62.2%; males 22.4%; 12 months or more: females 25.2%; males 6.6%). Family planning received little support from superiors (21.2% much to very much support) and 45.6% reported having experienced problems with their return to work or career advancement. Almost 60% of the participants did not have any specific working time models in their own hospital for employees with children who need to be cared for. CONCLUSION: In order to implement a work-life balance for physicians, changes are first and foremost necessary on the part of the institutions. In addition, the respective superiors must rethink in order to enable a parallelization of these two areas of their employees' lives. However, young physicians must also rethink their view of this issue. Demanding changes in labor law while continuing traditional family constellations at home does not seem to do address this issue adequately.

Improving Vascularization of Biomaterials for Skin and Bone Regeneration by Surface Modification: A Narrative Review on Experimental Research.

Artificial tissue substitutes are of great interest for the reconstruction of destroyed and non-functional skin or bone tissue due to its scarcity. Biomaterials used as scaffolds for tissue regeneration are non-vascularized synthetic tissues and often based on polymers, which need ingrowth of new blood vessels to ensure nutrition and metabolism. This review summarizes previous approaches and highlights advances in vascularization strategies after implantation of surface-modified biomaterials for skin and bone tissue regeneration. The efficient integration of biomaterial, bioactive coating with endogenous degradable matrix proteins, physiochemical modifications, or surface geometry changes represents promising approaches. The results show that the induction of angiogenesis in the implant site as well as the vascularization of biomaterials can be influenced by specific surface modifications. The neovascularization of a biomaterial can be supported by the application of pro-angiogenic substances as well as by biomimetic surface coatings and physical or chemical surface activations. Furthermore, it was confirmed that the geometric properties of the three-dimensional biomaterial matrix play a central role, as they guide or even enable the ingrowth of blood vessels into a biomaterial.

[Complete Occlusion of the radial Artery by a cardiogenic Embolus in infective Endocarditis]. / Komplette Okklusion der Arteria radialis durch einen kardiogenen Embolus bei infektiöser Endokarditis.

We present a case of septic embolization of the right radial artery by a cardiogenic embolus resulting from infective endocarditis. After the first suspicion of a palmar forearm phlegmon due to tenosynovitis was voiced, surgery revealed a long-segment occlusion of the radial artery. We resected the thrombosed part of the artery and reconstructed the latter with a vein interposition graft. Further diagnostic evaluation by echocardiography revealed vegetations on the anterior mitral leaflet. Reconstruction of the mitral valve was performed by annuloplasty.

Facilitation of adhesion and spreading of endothelial cells on silicone oxide-coated dacron material by microwave-excited low-pressure plasma.

OBJECTIVES: Autologous transplants are still the means of choice for bypass surgery. In addition to good tolerability, there is a reduced thrombogenicity and fewer neointima hyperplasia compared to artificial materials. However, since viable transplants are limited, attempts are being made to improve existing artificial vascular prosthesis material. Next to the reduction of thrombogenicity, a rapid endothelialization of the vascular graft should reduce intimal hyperplasia and thus prevent stenoses. The effect of newly developed silicon oxide coatings on the growth of endothelial cells was therefore the goal of this work in a cell culture study. METHODS: A woven, uncoated polyethylene terephthalate (PET) vessel prosthesis was used. The coating process was carried out in a low-pressure plasma reactor in a multi-step process. After preparation of the vacuum chamber hexamethyldisiloxane (HDMSO) with oxygen was evaporated using argon plasma. By this an approx. 1 nm thin adhesion promoter layer was separated from plasma and HMDSO. The silicone oxide barrier layer was applied to the PET vessel samples. The carbon content of the layer could be selectively altered by changing the HMDSO oxygen flow ratio, resulting in coatings of 100 nm, 500 nm, and 1,000 nm. In addition, two different oxygen-to-HMDSO ratios were used. To achieve a carbon coating as low as possible, the ratio was set to 200:1. A carbon-rich layer was obtained with the 1:1 setting. The various coatings were then examined for their surface texture by scanning electron microscopy (SEM) as well as by cell culture experiments for cell viability and growth using EA.hy 926 cells. RESULTS: SEM showed no changes in the surface morphology; however a layer thickness of 1,000 nm showed peeled off coating areas. Alamar blue assays showed a significantly higher metabolic activity (p=0.026) for the coating 500 nm, ratio 200:1 compared to untreated control samples and a significantly lower metabolic activity (p=0.037) of the coating 500 nm, ratio 1:1 compared to the coating 500 nm, ratio 200:1. This underlines the apparent tendency of the 1:1 coating to inhibit the metabolic activity of the cells, while the 200:1 coating increases the activity. Fluorescence microscopy after calcein acetoxymethyl ester (AM) staining showed no significant difference between the different coatings and the uncoated PET material. However, a tendency of the increased surface growth on the coating 500 nm, ratio 200:1, is shown. The coatings with the ratio 1:1 tend to be less densely covered. CONCLUSIONS: The results of this work indicate a great potential in the silicon coating of vascular prosthesis material. The plasma coating can be carried out easy and gently. Cell culture experiments demonstrated a tendency towards better growth of the cells on the 200:1 ratio coating and a poorer growth on the carbon-rich coating 1:1 compared to the uncoated material. The coating with silicon oxide with a thickness of 500 nm and an oxygen-HMDSO ratio of 200:1, a particularly low-carbon layer, appears to be a coating, which should therefore be further investigated for its effects on thrombogenicity and intimal hyperplasia.

Wound Healing and Therapy in Soft Tissue Defects of the Hand and Foot from a Surgical Point of View.

Wounds and tissue defects of the hand and foot often lead to severe functional impairment of the affected extremity. Next to general principles of wound healing, special functional and anatomic considerations must be taken into account in the treatment of wounds in these anatomical regions to achieve a satisfactory reconstructive result. In this article, we outline the concept of wound healing and focus on the special aspects to be considered in wounds of the hand and foot. An overview of different treatment and dressing techniques is given with special emphasis on the reconstruction of damaged structures by plastic surgical means.

Effects of Extracorporeal Shock Waves on Microcirculation and Angiogenesis in the in vivo Wound Model of the Diver Box.

INTRODUCTION: Extracorporeal shock waves (ESWs) have been shown to have a positive effect on skin wound healing; however, little is known on the regeneration of the microcirculation and angiogenesis as well as the different application modes. METHODS: A total of 40 BALB/c mice were provided with dorsal skin fold chambers and were divided into 3 therapy groups (n = 30) and one control group (n = 10). The 3 therapy groups were treated with shock waves at different pulse rates (500-1,000 pulses/min) and application frequencies (day 0 and day 6 or day 0 only). Photographic documentation and intravital microscopy were carried out on day 1, 2, 4, and 6 after wounding. RESULTS: Using the newly developed Diver Box, shock waves could be applied in vivo without mechanical tissue damage. Shock wave therapy to skin wounds demonstrated to induce faster wound closure rates in the beginning than controls in groups with higher pulse rates and frequencies of the shock waves. Furthermore, the regeneration of microcirculation and perfusion in the healing skin was significantly improved after the application of, in particular, higher pulse rates as given by increased numbers of perfused capillaries and functional vessel density. The study of inflammation showed, especially in high-pulse ESW groups, higher leukocyte counts, and rolling leukocytes over time until day 6 as a response to the induction of inflammatory reaction after ESW application. Angiogenesis showed a marked increase in positive areas as given by sprouts, coils, and recruitments in all ESW groups, especially between days 4 and 6. CONCLUSION: The major findings of this trial demonstrate that ESW therapy to skin wounds is effective and safe. This is demonstrated by the initially faster wound closure rate, but later the same wound closure rate in the treatment groups than in controls. Furthermore, during the regeneration of microcirculation and perfusion in the healing skin, a significant improvement was observed after the application of, in particular, higher ESW pulse rates, suggesting an ESW-related increase in nutrient and oxygen supply in the wound tissue.

[Change of perception of aged male attractiveness by conventional or male facelift: 3D simulation study of a new facelift concept for men]. / Veränderung der Wahrnehmung männlicher Attraktivität im Alter durch Standard- oder männliche Gesichtsstraffung: 3D-Simulationsstudie eines neuen Facelift-Konzeptes für Männer.

BACKGROUND: Facelift is now the fourth most common aesthetic procedure in men. Facial ageing is very different in men and women. Therefore, individual techniques are used since a uniform concept for the surgical facelift in men does not exist. This study aims to evaluate a gender-specific facelift concept especially developed for men. MATERIAL AND METHODS: Women and men (n = 10 each) were subjected to a three-dimensional face scan and a subsequent simulation of a V-shaped lift vector (standard lift) and a new facelift concept especially for men in a double T shape (male lift). In an online survey with 262 participants, the simulated as well as the unchanged images were presented and the attributes masculinity, femininity, attractiveness and youthfulness were queried. Statistical models were used to identify attributes of lifting as well as other factors and differences between the simulations. RESULTS: Facelift changes are generally associated with a significant improvement in the attributes of youthfulness and attractiveness compared with unchanged control faces. As expected, a male lift leads to masculinisation, while a standard lift leads to feminisation, regardless of the sex of the subjects. The male lift led to higher values for the attribute attractiveness in male subjects, as did the standard lift in female subjects. The standard lift developed for women is indeed more suitable for women and is associated with a significantly higher probability for the attribute youthfulness, whereas this is not the case in the newly introduced male lift concept. CONCLUSION: The new facelift concept for male patients is significantly associated with masculinity and attractiveness, while the standard lift suitable for women is associated with significantly higher evaluations of femininity and youthfulness. The results of the SIMALIFT study are the first evidence of the need for a more differentiated, gender-specific approach to facelifting.

The Preferred Management of a Single-Digit Distal Phalanx Amputation.

BACKGROUND: Replantation of a single digit at the distal phalanx level is not routinely performed since it is technically challenging with questionable cost-effectiveness. The purpose of this study was to analyze international microsurgeons' clinical decisions when faced with this common scenario. METHODS: A survey of a right-middle finger distal phalanx transverse complete amputation case was conducted via online and paper questionnaires. Microsurgeons around the world were invited to provide their treatment recommendations. In total, 383 microsurgeons replied, and their responses were stratified and analyzed by geographical areas, specialties, microsurgery fellowship training, and clinical experiences. RESULTS: Among 383 microsurgeons, 170 (44.3%) chose replantation as their preferred management option, 137 (35.8%) chose revision amputation, 62 (16.2%) chose local flap coverage, 8 (2.1%) chose composite graft, and 6 (1.6%) favored other choices as their reconstruction method for the case study. Microsurgeons from the Asia-Pacific, Middle East/South Asia, and Central/South America regions tend to perform replantation (70.7, 68.8, and 67.4%, respectively) whereas surgeons from North America and Europe showed a lower preference toward replantation (20.5 and 26.8%, respectively p < 0.001). Having completed a microsurgery fellowship increased the attempt rate of replantation by 15.3% (p = 0.004). Clinical experience and the surgeons' specialties did not show statistical significance in clinical decision making. CONCLUSION: From the present study, the geographic preferences and microsurgery fellowship experience influence the method of reconstruction for distal phalanx amputation. Multiple factors are taken into consideration in selecting the most suitable reconstructive method for each case scenario. In addition to the technical challenges of the proposed surgery, the cost of the procedure and the type of facility needed are important variables in the decision making process.

Panta Rhei: Neovascularization, Angiogenesis and Nutritive Perfusion in Wound Healing.

BACKGROUND: In response to tissue damage, angiogenesis is an extremely dynamic process that is finely regulated by signals from cells, the surrounding extracellular matrix (ECM), and derived mediators. As the only process, angiogenesis remains of decisive importance in the context of the entire wound healing process and is subject to constant change. The dissolution of the endothelial basement membrane, the migration of endothelial cells, and the development of new capillary vessels during wound healing depend not only on the cells and cytokines present, but also on the production and organization of ECM components in the immediate wound. SUMMARY: Angiogenesis in wound healing can be divided into two main phases. During the pro-angiogenic phase at the beginning of wound healing, excessive neo-formation of blood vessels, some of which are poorly differentiated, occurs, which restore blood flow and thus nutritive perfusion as quickly as possible. This is followed by an anti-angiogenic phase in which the initially established vascular network undergoes a maturing process, which, however, is accompanied by a significant reduction in the number of vessels. Key Messages: Although many mechanisms and specific cell functions in wound healing have already been described, many underlying pathophysiological processes remain unknown. Because angiogenesis and its maturation is a very fast but also very long-lasting process, the understanding of the underlying mechanisms is of crucial importance. This article will give an overview of the current understanding and controversy in this sub-step of wound healing.

A Novel Technique for the Standardized Application of Shock Waves in Experimental Research: The Diver Box.

The Diver Box is designed to prevent impedance differences, energy loss or damage to neighboring structures caused by the use of shock waves with application gels. The Diver Box is an acrylic glass container filled with tempered water and includes a coupling membrane to prevent the impedance jump from air to water and to avoid the continuous propagation of shock waves into the tissue, maintaining wave dynamics. Different modes of extracorporeal shock waves can be applied to a mouse skin wound without energy loss and protected from harmful phase-reversed waves. Macroscopic changes were seen in only 5% to 12% of tested specimens. Hazardous phase reversal, back reflection and mechanical tissue damage can be avoided by use of the Diver Box, ensuring standardized extracorporeal shock wave application.

In-vivo monitoring of infection via implantable microsensors: a pilot study.

The most common complication after implantation of foreign material is infection, leading to implant failure and severe patient discomfort. Smoldering-infections proceed inapparently and might not get verified by radiological diagnostics. Early identification of this type of infection might significantly reduce the rate of complications. Therefore, we manufactured a microsensor strip in a hybrid of thin-film and laminate technology in a wafer-level process. It comprises electrochemical, amperometric microsensors for glucose, oxygen and lactate as well as an integrated reference electrode. Microsensors have been implanted in the mouse dorsal skin fold chamber, which got inoculated with a human-pathogen bacterial strain. A selective signal could be measured for all parameters and time points. The infection led to measurable changes of the wound environment as given by a decrease of the oxygen- as well as the glucose-concentration while the lactate concentration increased markedly over time. The given results in this study are the first hints on a promising new tool and should therefore be interpreted as a proof of the principle to show the functionality of the microsensors in an in vivo setting. These microsensors could be used to monitor smoldering infections of implantable foreign materials reducing foreign implant associated complications.

Localized eosinophilic fasciitis (Shulman's disease) as a differential diagnosis of nerve compression syndrome.

A 46-year-old man presented with clinical signs of nerve compression syndrome of his right ulnar nerve as confirmed by nerve conduction studies. Unexpectedly, clinical examination and magnetic resonance imaging (MRI) revealed a subcutaneous tumor of 5×2 cm above the ulnar groove. Surgical exploration and histopathology of biopsies demonstrated the nerve distended and entrapped into an eosinophilic, inflammatory tissue. This rare condition is consistent with localized eosinophilic fasciitis, with no systemic manifestations. There are reports of isolated forearm versions of the disease. However, none occurred with the entrapment of a peripheral nerve appearing as a peripheral nerve tumor, yet. Consequentially, the presented patient would not have benefitted from further surgical neurolysis or tumor debulking, as eosinophilic fasciitis is an inflammatory and systemic disease. The patient's symptoms decreased spontaneously after 4 weeks of postsurgical treatment, including nonsteroidal anti-inflammatory drugs (NSAIDs). Altogether, this case proved the necessity to regard even rare diseases as a potential cause of entrapment of peripheral nerves. This should lead surgeons to critical, differential diagnostic thinking and suggest that systemic diseases may be encountered during surgery due to their capability to mimic peripheral nerve tumors.

Skin Wound Healing: An Update on the Current Knowledge and Concepts.

BACKGROUND: The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. METHODS: For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. RESULTS: The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. CONCLUSION: Although wound healing mechanisms and specific cell functions in wound repair have been delineated in part, many underlying pathophysiological processes are still unknown. The purpose of the following update on skin wound healing is to focus on the different phases and to brief the reader on the current knowledge and new insights. Skin wound healing is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications.

[Assessment of the significance and the requirements of medical postdoctoral lecture qualifications in Germany by the assessment committees]. / Bewertung des Stellenwerts und der Voraussetzungen der medizinischen Habilitation in Deutschland durch die beurteilenden Kommissionen.

OBJECTIVE: The postdoctoral medical lecture qualification (Habilitation) represents the highest academic qualification in Germany, which is successfully completed by approximately 850 candidates in medicine and health sciences per year. However, there is only a limited number of respective academic positions available. In addition, structures in education and society have changed over the last years, challenging the importance of this specific German qualification. The aim of this study was to elicit the opinions of members of German habilitation committees concerning the requirements, processes and the overall importance of the postdoctoral medical lecture qualification. Furthermore we wanted to evaluate potential needs for reforms. METHODS: The online survey was conducted asking for biographic parameters, subjective ratings and potential needs for reforms concerning the postdoctoral medical lecture qualification (PLQ). RESULTS: The PLQ was rated high in significance by 71.3 % of the committee members. According to the medical understanding of the Humboldt triad (research, teaching, patient care), research (94.3 %) and teaching (89.7 %) have been rated as the most important requirements for a PLQ. Asked for the motivation to undertake a PLQ, 91.0 % of the members gave the joy of doing research, 78.2 % the joy of teaching and 65.5 % better career prospects perspectives as their reason. The recognition of a Ph.D. degree as being equivalent to a German PQL was clearly rejected by the survey respondents (58.6 %: no equivalence). The majority is against the abolition of the German PLQ. However, there is a definite desire for reform, preferably concerning internal obstacles such as the dependence on full professors, more transparency in the PLQ process, but also the demand for a federal standard PLQ regulation. CONCLUSION: From the committee members' point of view the German PLQ has still a role to play and, despite controversy, is still regarded as a timely qualification. However, there is clear-cut evidence for local, national and international reforms in order to create equality of opportunity for the candidates and to open up suitable career options.

Angiogenesis, cell differentiation and cell survival in tissue engineering and cancer research.

Recent medical advances lead to a growing demand for tissue engineering and regenerative medicine in the future. Tissue engineering and regenerative medicine aim to create substitute tissue or restore lost or impaired tissue by combining biological science with engineering techniques, whereas cancer research faces the challenge to identify and hinder aberrant and uncontrolled cell growth. These two seemingly opposing fields of research share fundamental communalities. This review focuses on the shared underlying biological processes. Exploring these mechanisms of tissue growth and homeostasis from different angles will allow for creative novel approaches for both areas of research.

A low-cost, small volume circuit for autologous blood normothermic perfusion of rabbit organs.

We have designed a laboratory extracorporeal normothermic blood perfusion system for whole organs (e.g., kidney) that achieves pulsatile flow, low levels of hemolysis, and a blood priming volume of 60 mL or less. Using this uniquely designed extracorporeal circuit, we have achieved perfusion of two isolated ex vivo constructs. In the first experiment, we successfully perfused a rabbit epigastric flap based on the femoral vessels. In the second experiment, we were able to perfuse the isolated rabbit kidney for 48 h (range for all kidneys was 12-48 h) with excellent urine output, normal arterial blood gasses at 24 h, and normal ex vivo kidney histology at the conclusion of the experiments. These parameters have not been achieved before with any known or previously published laboratory extracorporeal circuits. The study has implications for prolonged organ perfusion prior to transplantation and for tissue engineering of vascularized tissues, such as by the perfusion of decellularized organs.

Salinomycin increases chemosensitivity to the effects of doxorubicin in soft tissue sarcomas.

BACKGROUND: Chemotherapy for soft tissue sarcomas remains unsatisfactory due to their low chemosensitivity. Even the first line chemotherapeutic agent doxorubicin only yields a response rate of 18-29%. The antibiotic salinomycin, a potassium ionophore, has recently been shown to be a potent compound to deplete chemoresistant cells like cancer stem like cells (CSC) in adenocarcinomas. Here, we evaluated the effect of salinomycin on sarcoma cell lines, whereby salinomycin mono- and combination treatment with doxorubicin regimens were analyzed. METHODS: To evaluate the effect of salinomycin on fibrosarcoma, rhabdomyosarcoma and liposarcoma cell lines, cells were drug exposed in single and combined treatments, respectively. The effects of the corresponding treatments were monitored by cell viability assays, cell cycle analysis, caspase 3/7 and 9 activity assays. Further we analyzed NF-κB activity; p53, p21 and PUMA transcription levels, together with p53 expression and serine 15 phosphorylation. RESULTS: The combination of salinomycin with doxorubicin enhanced caspase activation and increased the sub-G1 fraction. The combined treatment yielded higher NF-κB activity, and p53, p21 and PUMA transcription, whereas the salinomycin monotreatment did not cause any significant changes. CONCLUSIONS: Salinomycin increases the chemosensitivity of sarcoma cell lines - even at sub-lethal concentrations - to the cytostatic drug doxorubicin. These findings support a strategy to decrease the doxorubicin concentration in combination with salinomycin in order to reduce toxic side effects.

Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations.

Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies "initial" and "final" passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations.