Initialin vivotesting of TPO-receptor agonist eltrombopag in osteosarcoma patient-derived xenograft models by the pediatric preclinical testing consortium
PEDIATRIC HEMATOLOGY AND ONCOLOGY
Authors: Nevil, Grace; Roth, Michael; Gill, Jonathan; Zhang, Wendong; Teicher, Beverly; Erickson, Stephen W.; Gatto, Gregory; Smith, Malcom; Kolb, E. Anders; Gorlick, Richard
Abstract
Eltrombopag is a small molecule, thrombopoietin receptor agonist approved for the treatment of patients with aplastic anemia and chronic immune thrombocytopenia. It is also a polyvalent cation chelator and inhibits leukemia cell proliferation via reduction of intracellular iron. Thein vivoefficacy of eltrombopag was tested against a panel of six Pediatric Preclinical Testing Consortium osteosarcoma xenografts at doses of 5 mg/kg/day (moderate dose) and 50 mg/kg/day (high dose). Eltrombopag, at moderate doses, failed to significantly improve event-free survival (EFS) in 6/6 models. At high doses, eltrombopag significantly prolonged EFS in 2/2 models, though the effect size was small. All models tested demonstrated progressive disease. While eltrombopag did not meaningfully inhibit osteosarcoma growth, it also did not stimulate tumor growth, suggesting it may be safely investigated as a supportive care agent to enhance platelet recovery post chemotherapy.
Influence of Smoking on Thyroid Function in Japanese Subjects: Longitudinal Study for One Year of On-Off Smoking
JOURNAL OF THE ENDOCRINE SOCIETY
Authors: Nakajima, Yasuyo; Yamada, Sayaka; Nishikido, Ayaka; Katano-Toki, Akiko; Ishida, Emi; Akuzawa, Masako; Sakamaki, Koji; Yamada, Eijiro; Saito, Tsugumichi; Ozawa, Atsushi; Okada, Shuichi; Shimomura, Yohnosuke; Kobayashi, Isao; Andou, Yoshitaka; Yamada, Masanobu
Abstract
Context: We previously identified factors affecting thyroid status, including sex, age, and smoking. Objective: In the current study, we increased the number of subjects examined and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab), in Japanese patients with euthyroxinemia and serum free T4 levels within the normal range. Participants: A total of 12,289 subjects who underwent health checkups were analyzed in a cross-sectional and longitudinal study. Results: The mean age of subjects was 50 +/- 10 years (age range: 21 to 88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese subjects with euthyroxinemia. Mean serum TSH levels were significantly lower in the smoking group than in the nonsmoking group except for women older than 50 years. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both sexes; however, smoking did not affect free T4 levels or positivity for TPO-Ab. Among men, the rate of smokers was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%; P < 0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels 1 year after the start of smoking in men (P < 0.05). Conclusion: Because smoking appeared to lower serum TSH levels in Japanese subjects with euthyroxinemia, their smoking status warrants careful consideration when evaluating subclinical thyroid function. Copyright (C) 2019 Endocrine Society