BACKGROUND: Recently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure. METHODS: HT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay. RESULTS: Both taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent. CONCLUSIONS: Beside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.
Antineoplastic Agents , Colonic Neoplasms , Thiadiazines , Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Humans , Oxaliplatin , Taurine/analogs & derivatives , Taurine/pharmacology , Thiadiazines/pharmacology , Tumor Microenvironment
Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/- 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung.
Insulin Secretion/physiology , Insulin/biosynthesis , Islets of Langerhans Transplantation/methods , Islets of Langerhans/metabolism , Pulmonary Alveoli/surgery , Administration, Inhalation , Aerosols/administration & dosage , Animals , Blood Glucose/analysis , Diabetes Mellitus, Type 1/therapy , Glucose/administration & dosage , Glucose/metabolism , Swine
Due to the ease and increased volume of global interaction, it remains unclear whether the current coronavirus disease (COVID-19) pandemic will be a one-off event or whether the world is at risk of recurrent pandemics as a result of globalization. To address this important issue, the present study assessed the risk of a possible future Ebola pandemic. The risk profile of Hubei province in China was compared with that of the Democratic Republic of Congo (DRC) in terms of travel and infrastructure, since DRC is considered a major epicenter for Ebola outbreaks. Recurrence patterns of previous Ebola outbreaks were analyzed in a cumulative outbreak model. Internationally available data on air traffic, flight destinations, passenger numbers, population density, distribution and domestic traffic routes were all analyzed and compared between the DRC and Hubei province. DRC is a major epicenter for Ebola outbreaks, with 13 recorded outbreaks from 1976 until 2020. International airports at both Kinshasa, the capital city of the DRC and Wuhan, the capital city of Hubei province, are heavily frequented destinations and represent major transfer hubs on their respective continents. Volumes of flights to and from extracontinental destinations account for <25% of total flights at both airports with similar total international passenger volumes. However, the volume of domestic commuting by aviation is >30-fold higher at Hubei province compared with that of the DRC. This finding is also reflected by the higher population density and homogeneity in terms of population per square kilometer in Hubei. Following the analysis of decades of Ebola reports, it became evident that the DRC remains a hotspot for potential Ebola outbreaks in the future due to constantly recurrent local outbreaks. In terms of the international aviation network, numerous important similarities between Kinshasa and Hubei Province were observed as regards connectivity. The present comparative analysis extends beyond biological factors underlying Ebola and COVID-19 transmissions and confirms that the DRC, Kinshasa in particular, is not a remote location. Although internal commuting and population density may be lower in the DRC compared with those in Hubei province, integration into the international aviation network is similarly extensive. The international community must increase its focus and efforts in preventing another possible global pandemic commencing in Africa, and in particular the DRC.
