We show that the surface gravity of a transiting extrasolar planet can be calculated from only the spectroscopic orbit of its parent star and the analysis of its transit light curve. This does not ...require additional constraints, such as are often inferred from theoretical stellar models or model atmospheres. The surface gravity of the planet can therefore be measured precisely and from only directly observable quantities. We outline the method and apply it to the case of the first known transiting extrasolar planet, HD 209458b. We find a surface gravity of gp= 9.28 ± 0.15 m s−2, which is an order of magnitude more precise than the best available measurements of its mass, radius and density. This confirms that the planet has a much lower surface gravity than that predicted by published theoretical models of gas giant planets. We apply our method to all 14 known transiting extrasolar planets and find a significant correlation between surface gravity and orbital period, which is related to the known correlation between mass and period. This correlation may be the underlying effect as surface gravity is a fundamental parameter in the evaporation of planetary atmospheres.
We show that the surface gravity of a transiting extrasolar planet can be calculated from only the spectroscopic orbit of its parent star and the analysis of its transit light curve. This does not ...require additional constraints, such as are often inferred from theoretical stellar models or model atmospheres. The planet's surface gravity can therefore be measured precisely and from only directly observable quantities. We outline the method and apply it to the case of the first known transiting extrasolar planet, HD 209458b. We find a surface gravity of g_p = 9.28 +/- 0.15 m/s, which is an order of magnitude more precise than the best available measurements of its mass, radius and density. This confirms that the planet has a much lower surface gravity that that predicted by published theoretical models of gas giant planets. We apply our method to all fourteen known transiting extrasolar planets and find a significant correlation between surface gravity and orbital period, which is related to the known correlation between mass and period. This correlation may be the underlying effect as surface gravity is a fundamental parameter in the evaporation of planetary atmospheres.
Background
Systemic mastocytosis (SM) is characterized by abnormal proliferation and accumulation of neoplastic mast cells. Patients (pts) with SM are treated with recombinant interferon-alpha or ...cladribine. Responses to these agents are poor. Malignant mast cells in SM carry, in most cases, a mutation involving codon 816 of the c-KIT gene (D816V) resulting in constitutively activated c-kit receptor tyrosine kinase believed to be important for disease progression. Agents that antagonize this mutated form of c-kit may have clinical benefit in SM. Dasatinib is one such agent, proven effective in pre-clinical in vitro and in vivo models of SM.
Study Design
In pilot Phase II trial for SM, Dasatinib was administered at 70mg PO BID. Response was assessed after minimum of 3 months (3 cycles) of therapy. Therapy was discontinued in pts who showed no response after 6 cycles of therapy. Response was evaluated following guidelines proposed by Valent et al. (Leuk Res. 25;603–625, 2001). In addition, all symptoms related to SM were recorded and monitored.
Results
Thus far, a total of 30 pts have been treated; 24 are evaluable for response and toxicity, including 6 with aggressive SM (ASM), 4 with SM and associated hematologic non-mast cell disease (SM-AHNMD; 2 with chronic myelomonocytic leukemia and one each with myelofibrosis SM-MF; JAK2 mutation positive and abnormal cytogenetics and hypereosinophilic syndrome SM-HES; FIP1L1-PDGFRa negative) and 14 with indolent SM (ISM) with uncontrolled symptoms despite optimal supportive care measures. Median age is 57 years (range, 35–73); these were 10 males and 14 females; time from diagnosis to dasatinib therapy 49 months (range, 0–233), performance status 1 in 23 and 2 in 1 pt. Eleven patients were previously treated: imatinib mesylate in 6; denileukin diftitox in 4; and erythropoietin, interferon-alpha, or cladribine in 2 each. One pt, who had undergone splenectomy, had hepatomegaly prior to start of therapy. Median Hb 12.4g/dL (range, 8.5–15.4), WBC 6.7×109/L, (range, 3.5–53.3), and platelets 263×109/L (range, 60–377); no patient was transfusion dependent. Percent bone marrow mast cell varied from <10% in 9 pts, to 60% in 4 pts; blood tryptase level was ≤20ng/mL (not significant) in 7 pts and >200ng/mL (upper limit of the test) in 7 pts. A total of 94 cycles of therapy were administered. The median number of cycles was 4 (range, 1–8). Ten patients stopped therapy: 1 due to progression of AHNMD to acute leukemia, 1 lost a response (symptomatic improvement), 2 had no response after 3 months of therapy, and 6 due to toxicity. No grade 4 toxicity was observed. Twelve patients decreased the dose of dasatinib to 50mg PO BID, of which four to 40mg PO BID. Two patients (8%) achieved complete remission, one with SM-MF, and one with SM-HES. Both were c-KIT mutation negative and had low, not significant tryptase levels. Both were anemic (Hb 9.4g/dL) and failed erythropoietin therapy, and had abnormal WBC differential; one had low platelets (90×109/L). No significant response in % bone marrow mast cells (4 pts are too early in therapy) or blood tryptase levels have been observed in other patients so far. Symptoms related to SM improved significantly in 7 patients (29%).
Conclusion
Dasatinib is active in SM (overall response rate 37%). Updated clinical and molecular results will be presented.
From Field and Study Monson, Gale; Sams, James R.; Escalante, Rodolfo ...
The Condor (Los Angeles, Calif.),
05/1958, Letnik:
60, Številka:
3
Journal Article
PDF
