Intratumoral expression analysis reveals that OX40 and TIM-3 are prominently expressed and have variable associations with clinical outcomes in high grade serous ovarian cancer

Patients with ovarian cancer exhibit low response rates to anti-programmed cell death protein-1 (PD-1) based therapies, despite ovarian tumors demonstrating measurable immune responses. Therefore, the aim of the present study was to comparatively examine expression of notable immune co-stimulatory and co-inhibitory receptors in order identify the most abundant receptors that could potentially serve as therapeutic targets to enhance immunotherapy response in high grade serous ovarian cancer (HGSOC). The Cancer Genome Atlas (TCGA) was employed to compare levels of various HGSOC and pan-cancer cohorts. To confirm these findings at the protein level, immunofluorescence of select receptors was performed in 29 HGSOC patient tissue samples. TCGA and Kaplan Meier analysis was employed to determine the association of highly expressed immune receptors with clinical outcomes. TIM-3 and OX40 exhibited the highest expression in HGSOC at both the gene and protein level, with TIM-3 demonstrating highest levels on both CD8⁺ and CD4⁺ T cell subsets. Pan-cancer analysis determined that TIM-3 and OX40 levels were similar to those in immunotherapy-responsive cancers, while PD-1 exhibited much lower expression in HGSOC. Finally, OX40 was most strongly associated with improved patient survival. Overall, the current study suggested that TIM-3 and OX40 are frequently expressed intratumoral immune receptors in HGSOC and thus represent promising immune targets. Furthermore, the present analysis strongly suggested that OX40 was significantly associated with a longer survival and could potentially be utilized as a prognostic factor for improved patient outcomes in HGSOC.     

Progression of periodontal disease in the second/third molar region in subjects with asymptomatic third molars.

PURPOSE: To assess the change in periodontal status over time by periodontal probing depth (PD) in the third molar region. SUBJECTS AND METHODS: The data for these analyses are part of a study of subjects enrolled with 4 asymptomatic third molars with adjacent second molars in an institutional review board-approved longitudinal trial. Full mouth periodontal probing was conducted to determine periodontal status at baseline and follow-up. Panoramic radiographs were analyzed for angulation and degree of eruption of third molars. Subjects were categorized as those who exhibited at least a 2 mm change in periodontal PD between baseline and follow-up in the third molar region, the distal of a second molar or around a third molar, and those who did not exhibit a 2 mm or greater change. Subjects with and without changes in PD were compared with Cochran-Mantel-Haenzsel statistics. Level of significance was set at 0.05. RESULTS: Data from 254 subjects with at least 2 annual follow-up visits were available for analysis. Mean age at baseline was 27.5 years. Median follow-up from baseline to the second follow-up visit was 2.2 years (interquartile range 2.0, 2.6). At enrollment, 59% of the subjects had at least 1 PD > or =4 mm in the third molar region, one quarter had a PD > or =5 mm. Twenty-four percent of the subjects had at least 1 tooth that had an increased PD > or =2 mm in the third molar region at follow-up. If subjects had at least 1 PD > or =4 mm at baseline, 38% had at least 1 PD deepen by 2 mm or more at follow-up. Only 3% of those who had all teeth with a PD of less than 4 mm at baseline exhibited a change of > or =2 mm (P < .001). CONCLUSION: Increased periodontal PDs > or =2 mm were often found in the third molar region for asymptomatic subjects with at least 1 PD > or =4 mm at enrollment, clinical measures that indicated increased periodontal pathology, and a deteriorating periodontal condition.     

Effects of fibronectin pretreatment on cardiovascular, acid-base, metabolic, and organ function indices during endotoxin shock in the dog

Selected hemodynamic, pulmonary, acid-base, metabolic, hematological, and serum chemistry parameters were monitored for 6 hr in two groups of anesthetized dogs given an intravenous injection of Escherichia coli endotoxin. One group of animals was pretreated with purified human plasma fibronectin, and the other group received an equal volume of saline or dextrose. Between-group analysis showed that the fibronectin-treated group had significantly higher arterial blood pressure and glucose levels, and lower hemoglobin levels, at 4, 5, and 6 hr postendotoxin administration. This group also had higher arterial pH and base excess values at 5 and 6 hr postendotoxin administration. This study, along with others from our laboratory, suggests that exogenous administration of purified plasma fibronectin can be beneficial in the prophylactic treatment of impending sepsis or endotoxemia. However, the amount of benefit appears to be moderate. Whether combining fibronectin with other therapeutic modalities would be additive or synergistic cannot be ruled out and merits investigation.     

The sagittal sign. An early second trimester sonographic indicator of fetal gender

The sagittal sign for sonographic prediction of fetal gender in the early second trimester is described and its sensitivity and accuracy evaluated. One hundred eighty-four ultrasound examinations with gestational ages between 10 weeks and 20.5 weeks were performed in 165 patients over a three month period. Of the 165 patients included in this prospective study, the gender of the fetus in 105 patients was known as a result of amniocentesis or chorionic villus sampling. These 105 patients with known results were used to compare gender prediction based on conventional views with prediction based on the sagittal sign. The results of this study reveal the superiority of the sagittal view for predicting gender in the gestational age group of 14 weeks to 20.5 weeks.