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MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic.
Verstovsek, S, Chen, CC, Egyed, M, Ellis, M, Fox, L, Goh, YT, Gupta, V, Harrison, C, Kiladjian, JJ, Lazaroiu, MC, et al
Future oncology (London, England). 2021;(12):1449-1458
Abstract
Hallmark features of myelofibrosis (MF) are cytopenias, constitutional symptoms and splenomegaly. Anemia and transfusion dependency are among the most important negative prognostic factors and are exacerbated by many JAK inhibitors (JAKi). Momelotinib (MMB) has been investigated in over 820 patients with MF and possesses a pharmacological and clinical profile differentiated from other JAKi by inhibition of JAK1, JAK2 and ACVR1. MMB is designed to address the complex drivers of iron-restricted anemia and chronic inflammation in MF and should improve constitutional symptoms and splenomegaly while maintaining or improving hemoglobin in JAKi-naive and previously JAKi-treated patients. The MOMENTUM Phase III study is designed to confirm and extend observations of safety and clinical activity of MMB.
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Cage containing a biphasic calcium phosphate ceramic (Triosite) for the treatment of cervical spondylosis.
Cho, DY, Lee, WY, Sheu, PC, Chen, CC
Surgical neurology. 2005;(6):497-503; discussion 503-4
Abstract
BACKGROUND We evaluated the fusion efficacy and clinical outcomes of a cage containing a biphasic calcium phosphate ceramic (Triosite) in treating cervical spondylosis. METHODS We randomly divided 100 patients with cervical spondylosis undergoing anterior discectomy with interbody polyetheretherketone (PEEK) fusion into 2 groups in the past 2 years: group A (n = 50), PEEK cage containing a biphasic calcium phosphate ceramic (Triosite), and group B (n = 50), PEEK cage containing an autogenous iliac bone graft. We compared the fusion rate, fusion time, spinal curvature, and neuroforamen size between the 2 groups. We also compared excess operation time, excess blood loss, hospital stay, complications, and neurological recovery status between the groups. RESULTS The fusion rates were 57%, 67%, 77%, 82%, 92%, and 100% in group A and 81%, 86%, 95%, 95% 100%, and 100% in group B in the first 6 postoperative months. The fusion rate in group A was significantly lower than that in group B in the first 5 months after the procedure (P < .05 and P < .01, respectively), but the fusion rate reached 100% in both groups by the sixth month. Within the first 6 months, as the fusion level increased, the fusion rates reduced and time to fusion was delayed in both groups. There were no donor site complications in group A. However, 3 patients (6%) from group B experienced complications (1, wound infection; 1, numbness of thigh; and 1, subcutaneous hematoma) (P < .001). The hospital stay was shorter in group A (4.43 +/- 2.36 days) than in group B (7.00 +/- 3.77 days) (P = .001). The mean excessive blood loss and excessive operative time for an iliac bone graft in group B were 15 +/- 5 mL and 10 +/- 6 minutes. There was no statistical significance in spinal curve correction, neuroforamen enlargement, and neurological recovery. CONCLUSIONS A cage containing a biphasic calcium phosphate ceramic resulted in complete fusion by the sixth postoperative month, although the fusion rate was lower than that in a cage containing an autograft during the first 5 months after the operation and the time to fusion was delayed. Using a cage containing a biphasic calcium phosphate ceramic leads to a shorter hospital stay, less blood loss, shorter operative time, and no donor site complications. It seemed to be a good substitute for cervical spondylotic fusion.
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3.
The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants.
Fang, PC, Kuo, HK, Huang, CB, Ko, TY, Chen, CC, Chung, MY
Chang Gung medical journal. 2005;(10):708-15
Abstract
BACKGROUND Preterm infants may be born with deficits of both docosahexaenoic acid (DHA) and arachidonic acid (AA), but studies on supplementation of DHA and AA for preterm infants are limited. METHODS Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind, randomized, comparative study. Infants over 2000 g body weight, over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months. Sixteen infants received Neoangelac Plus with AA and DHA supplementation. Eleven infants received Neoangelac without AA and DHA supplementation. The babies had scheduled physical examinations and their cognitive development, visual acuity, and vital signs to be checked. Adverse events were also recorded. RESULTS The mean Mental Development Index (MDI) scores for the supplementation and non-supplementation groups were 96.1 +/- 8.6 and 91.7 +/- 10.4 respectively at 6 months and 98.7 +/- 8.0 and 90.5 +/- 6.9 respectively at 1 year. The mean Physical Development Index (PDI) scores of these two groups were 102.2 +/- 10.5 and 95.4 +/- 13.2 respectively at 6 months and 98.0 +/- 5.8 and 86.7 +/- 11.1 respectively at 1 year. By repeated measures ANOVA, significant differences existed between groups for MDI and PDI (p = 0.020 and 0.008). However, there were no differences in visual acuity, physical examination variables or vital signs between these two groups. No obvious adverse effects were observed during the study period. CONCLUSION These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA.
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A phase I/II study of infusional vinblastine with the P-glycoprotein antagonist valspodar (PSC 833) in renal cell carcinoma.
Bates, SE, Bakke, S, Kang, M, Robey, RW, Zhai, S, Thambi, P, Chen, CC, Patil, S, Smith, T, Steinberg, SM, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;(14):4724-33
Abstract
PURPOSE P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer. PATIENTS AND METHODS Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied. RESULTS The maximum-tolerated dose of vinblastine was 1.3 mg/m(2)/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m(2)/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by (99m)Tc-sestamibi imaging. A 15-fold range in cytochrome p450 activity was observed, as measured by midazolam clearance. No major responses were observed. CONCLUSIONS These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar.
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Modeling rhl quorum-sensing regulation on rhamnolipid production by Pseudomonas aeruginosa.
Chen, F, Chen, CC, Riadi, L, Ju, LK
Biotechnology progress. 2004;(5):1325-31
Abstract
The effect of autoinducer PAI2 on rhamnolipid (RL) production by Pseudomonas aeruginosa was evaluated using an rhlI null mutant of PAO1 added with PAI2 at various concentrations. A model has also been developed to describe the production kinetics regulated by the rhl quorum-sensing system in three steps: First, PAI2 combines with RhlR protein. Second, the activated complex RhlR:PAI2 triggers the transcription (and expression) of the rhlAB operon that encodes for rhamnosyltransferase. Finally, the enzyme catalyzes the RL synthesis. The model describes fairly well the experimental results/profiles from three different studies (this and two others reported in the literature). The overall picture predicted by the model is as follows: The induced enzyme synthesis proceeds at the highest rate following PAI2 addition. The rate decreases with time as the autoinducer is degraded. The enzyme concentration nonetheless continues to increase until reaching the plateau at the exhaustion of autoinducer. Higher added PAI2 concentrations thus give not only higher initial enzyme synthesis rates but also longer induced synthesis. As the enzyme concentration increases with time, the RL production rate also increases, resulting in an accelerated rise in RL concentrations initially. The increase in RL concentrations becomes linear at the exhaustion of PAI2. The best-fit model parameters obtained also provided important insights. To complex half of the intracellular RhlR proteins would require 1.61 microM PAI2, about half of the PAI2 concentration obtained in the stationary-phase culture of wild-type PAO1. On the other hand, to activate the rhamnosyltransferase synthesis at half of its maximum rate would require the binding of 39% of RhlR with PAI2. The maximum RL production rate of the culture was found to be 0.042 g/L.h, and the fully induced culture would require at least 1.61 h to synthesize the enzyme to the necessary level for producing RL at half of the maximum rate.
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6.
Effect of honey on naringin absorption from a decoction of the pericarps of Citrus grandis.
Hou, YC, Hsiu, SL, Yen, HF, Chen, CC, Chao, PD
Planta medica. 2000;(5):439-43
Abstract
To measure naringin/naringenin absorption of a decoction prepared from the pericarps of Citrus grandis and to investigate the effect of honey on naringin/naringenin absorption, six healthy males received 200 mL decoctions of untreated and honey-treated Pericarpium Citri Grandis in a randomized crossover design. The absorption was measured by renal recovery of naringenin glucuronides/sulfates over 48 hours. The contents of naringin/naringenin in 200 mL decoctions of untreated and honey-treated Pericarpium Citri Grandis were determined to be 261.5/23.8 mumol and 303.3/11.6 mumol, respectively. The mean cumulated renal excretion of naringenin glucuronides/sulfates after intake of these two decoctions were 74.8 mumol (26.2% of dose) and 49.8 mumol (15.8% of dose), respectively. Paired Student's t-test showed that the difference of the total renal recovery of naringin/naringenin between the two decoctions was significant. The results indicated that honey significantly reduced naringin/naringenin absorption by 33.4% in humans and suggested that honey treatment might alter the efficacy of Pericarpium Citri Grandis.