Prognostic factors associated with uterine sarcomas: the experience of a single institution.

Uterine sarcomas are infrequent and heterogeneous mesenchymal tumours, associated with aggressive characteristics and a poor clinical outcome. The aim of the study is to describe the prognostic factors associated with uterine sarcomas. The clinical records between 2000 and 2014 of women diagnosed with uterine sarcomas and initially treated surgically were reviewed. A histological comparison was performed. The overall survival (OS) and disease-free survival (DFS) were calculated and compared. Seventy-three women had surgery (12.3% had endometrial stromal sarcomas, 24.7% undifferentiated endometrial sarcomas, 49.3% leiomyosarcomas and 13.7% other subtypes). Complete cytoreduction had a mean DFS of 25.1 months, while the incomplete cytoreduction averaged in a DFS of 4.33 months (p = .04). The median five-year OS with a complete cytoreduction was not reached; the incomplete cytoreduction OS was 10.1 months (p = .002). Our data suggests that undifferentiated endometrial sarcomas have the lowest DFS (p = .004); while OS was negatively influence by stage IV (p < .001). Impact statement What is already known about this subject? Uterine sarcomas compared with the more common endometrial carcinomas (epithelial neoplasms), behave aggressively and are associated with a poorer prognosis. The rarity of uterine sarcoma has made it difficult to perform large studies to identify risk factors. What do the results of this study add? Complete cytoreduction improves the DFS and OS and may be a valuable prognostic factor. Poorer DFS and OS prognosis was observed in undifferentiated endometrial sarcomas. What are the implications of these findings for clinical practice and/or further research? Our results demonstrate the importance of an early diagnosis, and thus an early identification of disease that benefits from complete cytoreduction regardless of histology. For the advanced clinical stage of uterine sarcomas further research is necessary and participation in clinical trials should be encouraged.

Glucose and glutamine metabolism control by APC and SCF during the G1-to-S phase transition of the cell cycle

Recent studies have given us a clue as to how modulations of both metabolic pathways and cyclins by the ubiquitin system influence cell cycle progression. Among these metabolic modulations, an aerobic glycolysis and glutaminolysis represent an initial step for metabolic machinery adaptation. The enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and glutaminase-1 (GLS1) maintain a high abundance in glycolytic intermediates (for synthesis of non-essential amino acids, the use of ribose for the synthesis of nucleotides and hexosamine biosynthesis), as well as tricarboxylic acid cycle intermediates (replenishing the loss of mitochondrial citrate), respectively. On the one hand, regulation of these key metabolic enzymes by ubiquitin ligases anaphase-promoting complex/cyclosome (APC/C) and Skp1/cullin/F-box (SCF) has revealed the importance of anaplerosis by both glycolysis and glutaminolysis to overcome the restriction point of the G1 phase by maintaining high levels of glycolytic and glutaminolytic intermediates. On the other hand, only glutaminolytic intermediates are necessary to drive cell growth through the S and G2 phases of the cell cycle. It is interesting to appreciate how this reorganization of the metabolic machinery, which has been observed beyond cellular proliferation, is a crucial determinant of a cell’s decision to proliferate. Here, we explore a unifying view of interactions between the ubiquitin system, metabolic activity, and cyclin-dependent kinase complexes activity during the cell cycle

Glucose and glutamine metabolism control by APC and SCF during the G1-to-S phase transition of the cell cycle.

Recent studies have given us a clue as to how modulations of both metabolic pathways and cyclins by the ubiquitin system influence cell cycle progression. Among these metabolic modulations, an aerobic glycolysis and glutaminolysis represent an initial step for metabolic machinery adaptation. The enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and glutaminase-1 (GLS1) maintain a high abundance in glycolytic intermediates (for synthesis of non-essential amino acids, the use of ribose for the synthesis of nucleotides and hexosamine biosynthesis), as well as tricarboxylic acid cycle intermediates (replenishing the loss of mitochondrial citrate), respectively. On the one hand, regulation of these key metabolic enzymes by ubiquitin ligases anaphase-promoting complex/cyclosome (APC/C) and Skp1/cullin/F-box (SCF) has revealed the importance of anaplerosis by both glycolysis and glutaminolysis to overcome the restriction point of the G1 phase by maintaining high levels of glycolytic and glutaminolytic intermediates. On the other hand, only glutaminolytic intermediates are necessary to drive cell growth through the S and G2 phases of the cell cycle. It is interesting to appreciate how this reorganization of the metabolic machinery, which has been observed beyond cellular proliferation, is a crucial determinant of a cell's decision to proliferate. Here, we explore a unifying view of interactions between the ubiquitin system, metabolic activity, and cyclin-dependent kinase complexes activity during the cell cycle.