Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience.

Background: Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

Contrary effects of coenzyme Q10 and vitamin E after testicular ischemia/reperfusion in a rat model validated with glucose metabolism imaging.

OBJECTIVE: To evaluate the efficacy of antioxidants in cellular-level post-ischemia/reperfusion injury of the testis and to validate these effects with 18F-fluorodeoxyglucose positron emission tomography. METHODS: Fifty-six adult male rats were randomly divided into seven groups-Group 1: sham; Group 2: ischemia/reperfusion only group; Group 3: ischemia was induced and vitamin E (100 mg/kg) was administered intraperitoneally 30 min before reperfusion; Group 4: vitamin E was given intraperitoneally without ischemia/reperfusion; Group 5: ischemia was induced and coenzyme Q10 (10 mg/body weight) was administered intraperitoneally 30 min before reperfusion; Group 6: coenzyme Q10 was administered intraperitoneally without ischemia/reperfusion; Group 7: ischemia was induced and coenzyme Q10 + vitamin E was administered intraperitoneally 30 min before reperfusion. After detorsion, fluorodeoxyglucose was applied to all groups according to the animals' weight and fluorodeoxyglucose positron emission tomography was performed after 1 h. In pursuit of imaging, orchiectomy was performed for histopathological and biochemical evaluations. RESULTS: A significant effect of group on catalase, maximum standardized uptake value, and seminiferous tubule diameters (p < 0.005) was observed. According to this, combining ischemia/reperfusion with vitamin E increased the maximum standardized uptake value significantly higher than in all other groups; in addition, catalase was significantly higher than in Groups 4-6. Histopathological outcomes revealed that "sham" had significantly larger seminiferous tubule diameter than Groups 2-4. Also, "ischemia/reperfusion" was the only group which had significantly smaller seminiferous tubule diameters than Groups 6 and 7. CONCLUSION: In contrast to vitamin E, coenzyme Q10 provided remarkable regression of oxidative stress-induced enzymes and revealed consistent effects on histopathological outcomes, which were validated with fluorodeoxyglucose positron emission tomography imaging.

Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model.

INTRODUCTION: Mesenteric ischemia/reperfusion (I/R) injury is a serious clinical condition. There were a lot of experimental studies performed in the treatment of I/R injury. To our knowledge, this is the first experimental study with effects of sesamin on I/R injury model. We aimed to investigate the protective effect of sesamin on mesenteric I/R injury model. MATERIAL AND METHODS: A total of 32 male Sprague-Dawley rats were divided into four groups. Control group: superior mesenteric artery (SMA) exposed without clamping. I/R group: SMA was clamped for 60 min and then reperfused for 2 h. Sesamin group (S): 30 mg/kg sesamin were given for 5 days, and SMA exposed without clamping. I/R + S group: 30 mg/kg sesamin were given for 5 days, SMA was clamped for 60 min, and then reperfused for 2 h. Plasma and tissue oxidant parameters were investigated as well as histopathological evaluation. RESULTS: Plasma and tissue total antioxidant status (TAS) levels were significantly higher in I/R + S group compared to the rest (p < 0.005). The plasma TAS levels in I/R group was significantly low. The highest tissue TAS levels were detected in I/R + S group. The high levels of plasma and tissue TOS were found in I/R + S group. Plasma and tissue OSI levels were significantly higher in I/R group. Histopathologic evaluation showed that the mean level of intestinal tissue injury score in I/R group was 2.75 and 1.38 in I/R + S group. CONCLUSIONS: Sesamin helps to protect the intestinal tissue at the cellular level by reducing the oxidative stress and inflammation at both the plasma and tissue levels in the experimental I/R model.