ABSTRACT
Research on mitochondrial metabolism and respiration are rapidly developing areas, however, efficient and widely accepted methods for studying these in solid tumors are still missing. Here, we developed a new method without isotope tracing to quantitate time dependent mitochondrial citrate efflux in cell lines and human breast cancer samples. In addition, we studied ADP-activated respiration in both of the sample types using selective permeabilization and showed that metabolic activity and respiration are not equally linked. Three times lower amount of mitochondria in scarcely respiring MDA-MB-231 cells convert pyruvate and glutamate into citrate efflux at 20% higher rate than highly respiring MCF-7 mitochondria do. Surprisingly, analysis of 59 human breast cancers revealed the opposite in clinical samples as aggressive breast cancer subtypes, in comparison to less aggressive subtypes, presented with both higher mitochondrial citrate efflux and higher respiration rate. Additionally, comparison of substrate preference (pyruvate or glutamate) for both mitochondrial citrate efflux and respiration in triple negative breast cancers revealed probable causes for high glutamine dependence in this subtype and reasons why some of these tumors are able to overcome glutaminase inhibition. Our research concludes that the two widely used breast cancer cell lines fail to replicate mitochondrial function as seen in respective human samples. And finally, the easy method described here, where time dependent small molecule metabolism and ADP-activated respiration in solid human cancers are analyzed together, can increase success of translational research and ultimately benefit patients with cancer.
ABSTRACT
BACKGROUND: Thymic epithelial tumors are rare thoracic tumors for which pathological diagnosis is challenging due to the definition of multiple subtypes, tumor heterogeneity, and variations in interobserver reproducibility. In this study, we aimed at analyzing the quality of pathological reporting in line with the consistency between initial diagnosis and final diagnosis after expert review through a collaboration between the largest thoracic oncology center in Estonia, and one expert center in France. METHODS: Hospital electronic database and pathology databases from the Tallinn North Estonia Medical Centre were searched for thymic and mediastinal tumors from 2010 to 2017. Pathology specimens were referred to the Pathology Department of the Lyon University hospital. Overall, 55 tissue specimens from 49 patients were included. RESULTS: From pathology reports, tumor size, diagnosis, and invasion had been mentioned in ≥80% of cases, while resection status and staging were assessed in only 48% and 17% of cases, respectively. The initial diagnosis was consistent with that of the review in 60% of cases. Diagnostic concordance for thymoma subtypes was low (Cohen's kappa 0.34, 95% CI: 0.16-0.52). Overall, a major change in the management of 8 (16%) patients had to be made after pathological review: 3 patients had a normal thymus according to the reference centre, while thymoma B1 or B2 had been diagnosed locally; 5 additional patients had a final diagnosis of non-thymic tumor. CONCLUSIONS: Implementing structured pathology reports may help to decrease discrepancies in the diagnosis of thymic epithelial tumors. The development of expert networks is an opportunity to improve diagnosis and patient care, particularly in regard to rare cancers.
ABSTRACT
BACKGROUND: Attempts to relate patellar cartilage involvement to anterior knee pain (AKP) have yielded conflicting results. We determined whether the condition of the cartilage of the patella at the time of knee replacement, as assessed by the OARSI score, correlates with postsurgical AKP. PATIENTS AND METHODS: We prospectively studied 100 patients undergoing knee arthroplasty. At surgery, we photographed and biopsied the articular surface of the patella, leaving the patella unresurfaced. Following determination of the microscopic grade of the patellar cartilage lesion and the stage by analyzing the intraoperative photographs, we calculated the OARSI score. We interviewed the patients 1 year after knee arthroplasty using the HSS patella score for diagnosis of AKP. RESULTS: 57 of 95 patients examined had AKP. The average OARSI score of painless patients was 13 (6-20) and that of patients with AKP was 15 (6-20) (p = 0.04). Patients with OARSI scores of 13-24 had 50% higher risk of AKP (prevalence ratio = 1.5, 95% CI: 1.0-2.3) than patients with OARSI scores of 0-12. INTERPRETATION: The depth and extent of the cartilage lesion of the knee-cap should be considered when deciding between the various options for treatment of the patella during knee replacement.