ABSTRACT
We hypothesize that dosage compensation of critical genes arises from systems-level properties for cancer cells to withstand the negative effects of aneuploidy. We identified several candidate genes in cancer multiomics data and developed a biocomputational platform to construct a mathematical model of their interaction network with micro-RNAs and transcription factors, where the property of dosage compensation emerged for MYC and was dependent on the kinetic parameters of its feedback interactions with three micro-RNAs. These circuits were experimentally validated using a genetic tug-of-war technique to overexpress an exogenous MYC, leading to overexpression of the three microRNAs involved and downregulation of endogenous MYC. In addition, MYC overexpression or inhibition of its compensating miRNAs led to dosage-dependent cytotoxicity in MYC-amplified colon cancer cells. Finally, we identified negative correlation of MYC dosage compensation with patient survival in TCGA breast cancer patients, highlighting the potential of this mechanism to prevent aneuploid cancer progression.
ABSTRACT
Introduction: In recent years, the use of 3D printing in medicine has grown exponentially, but the use of 3D technology has not been equally adopted by the different medical specialties. Published 3D printing activity in general thoracic surgery is scarce and has been mostly limited to case reports. The aim of this report was to reflect on the results and lessons learned from a newly created multidisciplinary and multicenter 3D unit of the Spanish Society of Thoracic Surgery (SECT). Methods: This is a pilot study to determine the feasibility and usefulness of printing 3D models for patients with thoracic malignancy or airway complications, based on real data. We designed a point-of-care 3D printing workflow involving thoracic surgeons, radiologists with experience in intrathoracic pathology, and engineers with experience in additive manufacturing. Results: In the first year of operation we generated 26 three-dimensional models out of 27 cases received (96.3%). In 9 cases a virtual model was sufficient for optimal patient handling, while in 17 cases a 3D model was printed. Per pathology, cases were classified as airway stenosis after lung transplantation (7 cases, 25.9%), tracheal pathology (7 cases, 25.9%), chest tumors (6 cases, 22.2%) carcinoid tumors (4 cases, 14.8%), mediastinal tumors (2 cases, 7.4%) and Pancoast tumors (one case, 3.7%). Conclusion: A multidisciplinary 3D laboratory is feasible in a hospital setting, and working as a multicenter group increases the number of cases and diversity of pathologies thus providing further opportunity to study the benefits of the 3D printing technology in general thoracic surgery.
