CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10 facilitate chemotactic recruitment of TILs, and their intratumoral accumulation is a conceivable way to improve TIL-dependent immune intervention in cancer. However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian cancer (HGSC) is largely unknown. METHODS: One hundred and eighty four cases of HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using the ovarian cancer cell lines OV-MZ-6 and SKOV-3. RESULTS: High expression of CXCL9 and CXCL10 was associated with an approximately doubled overall survival (n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52; P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin E2 was identified as negative regulator of chemokine secretion, whereas COX inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy of ovarian cancer, suppressed NF-κB activation and inhibited chemokine release. CONCLUSION: Our results support the notion that CXCL9 and CXCL10 exert tumour-suppressive function by TIL recruitment in human ovarian cancer. COX inhibition by indomethacin, not by celecoxib, may be a promising approach to concomitantly improve immunotherapies.

Maternal correlates of growth in toddler vocabulary production in low-income families.

This study investigated predictors of growth in toddlers' vocabulary production between the ages of 1 and 3 years by analyzing mother-child communication in 108 low-income families. Individual growth modeling was used to describe patterns of growth in children's observed vocabulary production and predictors of initial status and between-person change. Results indicate large variation in growth across children. Observed variation was positively related to diversity of maternal lexical input and maternal language and literacy skills, and negatively related to maternal depression. Maternal talkativeness was not related to growth in children's vocabulary production in this sample. Implications of the examination of longitudinal data from this relatively large sample of low-income families are discussed.

Variation in predictors of primary care career choice by year and stage of training.

CONTEXT: It is not known whether factors associated with primary care career choice affect trainees differently at different times or stages of medical education. OBJECTIVE: To examine how role models, encouragement, and personal characteristics affect career choice at different stages (medical school vs residency) and periods (1994 vs 1997) of training. DESIGN: A split-panel design with 2 cross-sectional telephone surveys and a panel survey in 1994 and 1997. PARTICIPANTS: A national probability sample of fourth-year students (307 in 1994, 219 in 1997), 645 second-year residents in 1994, and 494 third-year residents in 1997. Of the fourth-year students interviewed in 1994, 241 (78.5%) were re-interviewed as third-year residents in 1997. MAIN OUTCOME MEASURE: Primary care (general internal medicine, general pediatrics, or family medicine) career choice. RESULTS: Having a primary care role model was a stronger predictor of primary care career choice for residents (odds ratio [OR], 18.0; 95% confidence interval [95% CI], 11.2 to 28.8 in 1994; OR, 43.7; 95% CI, 24.4 to 78.3 in 1997) than for students (OR, 6.5; 95% CI, 4.3 to 10.2; no variation by year). Likewise, peer encouragement was more predictive for residents (OR, 5.4; 95% CI, 3.3 to 8.9 in 1994; OR, 16.6; 95% CI; 9.7 to 28.4 in 1997) than for students (OR, 2.1; 95% CI, 1.3 to 3.2; no variation by year). Orientation to the emotional aspects of care was consistently associated with primary care career choice across stages and years of training. CONCLUSIONS: The effect of peer encouragement and role models on career choice differed for students and residents and, in the case of residents, by year of training, suggesting that interventions to increase the primary care workforce should be tailored to stage of training.