Transformation of normal cells into malignant tumor cells, a process termed carcinogenesis, depends on progressive acquisition of genetic alterations. These result in activation of protooncogenes or inactivation of tumor suppressor genes responsible for the loss of proliferative control in tumor cells and the failure to undergo cellular differentiation. The aim of our study was the identification of molecular regulators of carcinogenesis by studying gene expression during induction of cellular differentiation and quiescence in a three-dimensional (3D) cell culture model. Here, we report the discovery of a tumor suppressor gene located at chromosome 8p21.3-22 near marker D8S254. It is ubiquitously expressed in normal tissue and transiently up-regulated during initiation of cellular differentiation and quiescence in 3D cell culture. In contrast, mRNA expression was not detectable in tissue from pancreatic tumor and the pancreatic tumor cell line MIA PaCa-2. Recombinant expression in the tumor cell line MIA PaCa-2 inhibited proliferation, as shown by a 30% reduction of BrdU uptake after recombinant expression. Immunocytochemistry and Western blot analysis of subcellular fractions demonstrated a mitochondrial localization for the mature protein. In conclusion, we identified a tumor suppressor gene at chromosome 8p21.3-22, encoding a mitochondrial protein, controlling cellular proliferation.
Background
During the first wave of the COVID-19 pandemic, German health care centres were restructured for the treatment of COVID-19 patients. This was accompanied by the suspension of the surgical programme. The aim of the survey was to determine the effects of COVID-19 on surgical care in non-university hospitals in Germany.
Methods
This cross-sectional study was based on an anonymous online survey, which was accessible from April 24th to May 10th, 2020 for surgeons of the Konvent der leitenden Krankenhauschirurgen (Convention of leading Hospital Surgeons) in Germany. The analysis comprised of 22.8% (n = 148/649) completed surveys.
Results
Communication and cooperation with authorities, hospital administration and other departments were largely considered sufficient. In the early phase of the COVID-19 pandemic, 28.4% (n = 42/148) of the respondents complained about a short supply of protective equipment available for the hospital staff. 7.4% (n = 11/148) of the participants stated that emergency operations had to be postponed or rescheduled. A decreased quantity of emergency surgical procedures and a decreased number of surgical emergency patients treated in the emergency room was reported in 43.9% (n = 65/148) and 63.5% (n = 94/148), respectively. Consultation and treatment of oncological patients in the outpatient clinic was decreased in 54.1% (n = 80/148) of the surveyed hospitals. To increase the capacity for COVID-19 patients, a reduction of bed and operating room occupancy of 50.8 ± 19.3% and 54.2 ± 19.1% were reported, respectively. Therefore, 90.5% (n = 134/148) of all participants expected a loss of revenue of 28.2 ± 12.9% in 2020.
Conclusion
The first wave of the COVID-19 pandemic had a significant impact on surgical care in Germany. The reduction in the bed and the operating room capacity may have lead to considerable delays in urgent and semi-elective surgical interventions. In addition to the risk of worsening patient care, we anticipate severe financial damage to the clinics in 2020 and beyond. National and supranational planning is urgently needed to ensure the surgical care of patients during the ongoing COVID-19 pandemic.
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