-
1.
Arsenic Combined With All-Trans Retinoic Acid for Pediatric Acute Promyelocytic Leukemia: Report From the CCLG-APL2016 Protocol Study.
Zheng, H, Jiang, H, Hu, S, Liao, N, Shen, D, Tian, X, Hao, G, Jin, R, Li, J, Fang, Y, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021;(28):3161-3170
-
-
Free full text
-
Abstract
PURPOSE Arsenic combined with all-trans retinoic acid (ATRA) is the standard of care for adult acute promyelocytic leukemia (APL). However, the safety and effectiveness of this treatment in pediatric patients with APL have not been reported on the basis of larger sample sizes. METHODS We conducted a multicenter trial at 38 hospitals in China. Patients with newly diagnosed APL were stratified into two risk groups according to baseline WBC count and FLT3-ITD mutation. ATRA plus arsenic trioxide or oral arsenic without chemotherapy were administered to the standard-risk group, whereas ATRA, arsenic trioxide, or oral arsenic plus reduced-dose anthracycline were administered to the high-risk group. Primary end points were event-free survival and overall survival at 2 years. RESULTS We enrolled 193 patients with APL. After a median follow-up of 28.9 months, the 2-year overall survival rate was 99% (95% CI, 97 to 100) in the standard-risk group and 95% (95% CI, 90 to 100) in the high-risk group (P = .088). The 2-year event-free survival was 97% (95% CI, 93 to 100) in the standard-risk group and 90% (95% CI, 83 to 96) in the high-risk group (P = .252). The plasma levels of arsenic were significantly elevated after treatment, with a stable effective level ranging from 42.9 to 63.2 ng/mL during treatment. In addition, plasma, urine, hair, and nail arsenic levels rapidly decreased to normal 6 months after the end of treatment. CONCLUSION Arsenic combined with ATRA is effective and safe in pediatric patients with APL, although long-term follow-up is still needed.
-
2.
The Association of Longitudinal Serum Uric Acid and All-Cause Mortality in Incident Peritoneal Dialysis Patients.
Chang, W, Zhang, W, Wang, X, Liu, Y, Han, Y, Tu, Y, Uchida, S
Blood purification. 2019;(1-3):185-192
Abstract
BACKGROUND Time-averaged uric acid (TA-UA) value was calculated to investigate the association of longitudinal UA and all-cause mortality in incident peritoneal dialysis (PD) patients. METHODS Three hundred PD patients were divided into 3 groups based on the serum TA-UA level (Group 1: < 6 mg/dL; Group 2: 6-8 mg/dL; Group 3: ≥8 mg/dL). Hazards ratio (HR) of all-cause mortality was calculated. Logistic regression was conducted to identify the associated clinical factors of lower and higher TA-UA level. RESULTS Increased HRs for death existed in Group 1 and Group 3 compared with Group 2 (HR 3.24, 95% CI 1.25-8.39, p = 0.016; HR 4.69, 95% CI 1.24-17.72, p = 0.023). Lower residual renal function, lower albumin, and higher high-density lipoprotein cholesterol were related to the lower serum TA-UA. Higher body mass index and higher C-reactive protein were associated with higher serum TA-UA in PD patients. CONCLUSION Both TA-UA < 6 and ≥8 mg/dL increased the all-cause mortality in incident PD patients.
-
3.
Circulating Heme Oxygenase-1 and Complement Activation in Transplant-Associated Thrombotic Microangiopathy.
Pan, T, Qi, J, You, T, Han, S, Yang, L, Miao, W, Wu, D, Ruan, C, Zhu, L, Han, Y
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019;(8):1486-1491
Abstract
Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication in patients after hematopoietic stem cell transplantation. The pathogenesis of TA-TMA is still unclear. Previous studies showed that complement activation plays an important role in the development of TA-TMA. However, no data showed which kind of complement component triggers this process. In this study we found that heme oxygenase-1, which could induce decay-accelerating factor (DAF) and inhibit the membrane-attack complex, was significantly decreased in patients with TA-TMA. DAF levels in the TA-TMA group were in line with the levels in the myocardial infarction group but were lower than levels in the healthy, noncomplication, infection, and graft-versus-host disease groups (P < .05). Human umbilical vein endothelial cells (HUVECs) incubated with TA-TMA plasma showed lower DAF levels compared with that incubated with normal human plasma. Notably, treatment with N-acetylcysteine (NAC), a drug against oxidation, increased the level of DAF. NAC could also inhibit complement activation in HUVECs incubated with TA-TMA plasma. Taken together, we propose that NAC represents a new potential therapy for patients facing TA-TMA.
-
4.
Gastrointestinal Tolerance of D-Allulose in Healthy and Young Adults. A Non-Randomized Controlled Trial.
Han, Y, Choi, BR, Kim, SY, Kim, SB, Kim, YH, Kwon, EY, Choi, MS
Nutrients. 2018;(12)
Abstract
D-allulose has recently received attention as a sugar substitute. However, there are currently no reports regarding its association with gastrointestinal (GI) tolerance. Thus, we performed a GI tolerance test for D-allulose in order to establish its daily acceptable intake level. When the dose of D-allulose was gradually increased in steps of 0.1 g/kg·Body Weight (BW) to identify the maximum single dose for occasional ingestion, no cases of severe diarrhea or GI symptoms were noted until a dose of 0.4 g/kg·BW was reached. Severe symptoms of diarrhea were noted at a dose of 0.5 g/kg·BW. Similarly, the GI tolerance test did not show any incidences of severe diarrhea or GI symptoms until a dose of 0.5 g/kg·BW was reached. A correlation analysis of the GI tolerance test for D-allulose and sugar revealed significantly higher frequencies of symptoms of diarrhea (p = 0.004), abdominal distention (p = 0.039), and abdominal pain (p = 0.031) after D-allulose intake. Increasing the total daily D-allulose intake gradually to 1.0 g/kg·BW for regular ingestion resulted in incidences of severe nausea, abdominal pain, headache, anorexia, and diarrheal symptoms. Based on these results, we suggest a maximum single dose and maximum total daily intake of D-Allulose of 0.4 g/kg·BW and 0.9 g/kg·BW, respectively.
-
5.
Risk of major adverse cardiovascular events in subjects with asymptomatic mild carotid artery stenosis.
Kwon, H, Kim, HK, Kwon, SU, Lee, SW, Kim, MJ, Park, JW, Noh, M, Han, Y, Kwon, TW, Cho, YP
Scientific reports. 2018;(1):4700
Abstract
This study aimed to test the hypothesis that the risk of major adverse cardiovascular events (MACE) is similar for subjects with asymptomatic mild and moderate carotid artery stenosis (CAS). We enrolled a total of 453 subjects with asymptomatic CAS (30-69%) detected on baseline screening Doppler ultrasound (DUS) examination between January 2008 and December 2010. The follow-up DUS findings and MACE occurrence (fatal or nonfatal myocardial infarction or stroke and all-cause mortality) were compared between subjects with mild (30-49%) and moderate (50-69%) CAS during the 8-year follow-up period. There was no significant difference in the occurrence of MACE between subjects with mild (n = 289) and moderate (n = 164) CAS (13.8% vs. 15.9%, respectively; p = 0.56), although there was a nonsignificant trend toward an increased risk of major ipsilateral stroke in subjects with moderate CAS (1.4% vs. 4.3%; p = 0.06). Multivariate regression analysis indicated that worsening CAS was independently associated with MACE occurrence (hazard ratio [HR], 4.40; 95% confidence interval [CI], 2.65-7.27; p < 0.01), whereas an increased serum high-density lipoprotein cholesterol level was correlated with a decreased risk of MACE (HR, 0.42; 95% CI, 0.23-0.75; p < 0.01). The cumulative risk of MACE in subjects with asymptomatic mild CAS is similar to that in subjects with asymptomatic moderate CAS.
-
6.
Assessment of Drug-Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects.
Ayalasomayajula, S, Pan, W, Han, Y, Yang, F, Langenickel, T, Pal, P, Zhou, W, Yuan, Y, Rajman, I, Sunkara, G
European journal of drug metabolism and pharmacokinetics. 2017;(2):309-318
Abstract
BACKGROUND AND OBJECTIVE LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokinetic drug-drug interaction between atorvastatin and LCZ696 was evaluated. METHODS This was an open-label, three-period, single-sequence study in 28 healthy Chinese male subjects wherein LCZ696 200 mg was administered twice daily for 5 days in period 1. Following a washout period, atorvastatin 80 mg was administered once daily for 4 days (period 2) and subsequently co-administered with LCZ696 200 mg for 5 days (period 3). Serial plasma samples were collected to determine pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan) and atorvastatin and its metabolites. RESULTS Atorvastatin co-administration had no effect on the pharmacokinetics of LBQ657, while the AUCτ,ss and C max,ss of sacubitril increased by 30 and 19 %, respectively, and the corresponding values for valsartan decreased by 19 and 9 %, respectively. Co-administration with LCZ696 increased C max,ss of atorvastatin, o-hydroxyatorvastatin, and p-hydroxyatorvastatin by 74, 68, and 108 %, respectively, and the AUCτ,ss of corresponding analytes increased by 34, 22, and 26 %, respectively. CONCLUSIONS While atorvastatin had no significant impact on the pharmacokinetics of LCZ696 analytes upon co-administration, the C max of atorvastatin and its metabolites increased twofold, with a marginal increase in AUC (<1.3-fold). Multiple-dose administration of LCZ696 200 mg twice daily and atorvastatin 80 mg once daily either alone or in combination was generally safe and well tolerated in healthy subjects.
-
7.
Longitudinal increase in vitamin D binding protein levels after initiation of tenofovir/lamivudine/efavirenz among individuals with HIV.
Hsieh, E, Fraenkel, L, Han, Y, Xia, W, Insogna, KL, Yin, MT, Zhu, T, Cheng, X, Li, T
AIDS (London, England). 2016;(12):1935-42
-
-
Free full text
-
Abstract
OBJECTIVE To examine longitudinal change in vitamin D binding protein (DBP) levels during the first year after initiation of tenofovir disoproxil fumarate (TDF)/lamivudine/efavirenz and compare these findings with concurrent changes in markers of skeletal metabolism. DESIGN Secondary analysis of plasma samples collected from an ongoing multicenter clinical trial. METHODS Plasma samples collected at 0, 24, and 48 weeks after initiation of TDF + lamivudine + efavirenz from 134 adult participants enrolled in a multicenter randomized trial were analyzed. Data regarding sociodemographic and clinical characteristics were obtained as part of the parent study. Laboratory analyses included plasma DBP, intact parathyroid hormone, total 25-hydroxy vitamin D, phosphorus, the bone resorption marker collagen type 1 cross-linked C-telopeptide, and the bone formation marker total procollagen type 1 N-terminal propeptide. Repeated measures analysis of variance was used to measure changes in biomarkers over time. RESULTS Our sample included 108 men and 26 women (mean age 33.6 ± 9.6 years). Median levels of DBP increased significantly from baseline to 48 weeks [154 (91.8-257.4) versus 198.3 (119.6-351.9) μg/ml, P < 0.001]. A concurrent rise in intact parathyroid hormone levels was observed over the same period [32.3 (24.4-40.9) versus 45.2 (35.1-60.4) pg/ml, P < 0.001]; however, 25-hydroxy vitamin D and phosphorus levels remained stable. Bone resorption and formation markers rapidly increased from 0 to 24 weeks, followed by a slight decline or plateau, but remained significantly elevated at 48 weeks (P < 0.001). CONCLUSION Our study provides longitudinal data supporting a potential role for DBP in bone loss associated with TDF-based therapy. Further research to elucidate the mechanistic pathways and clinical impact of these findings is warranted.
-
8.
Changes in Mitochondrial Toxicity in Peripheral Blood Mononuclear Cells During Four-Year Administration of Entecavir Monotherapy in Chinese Patients with Chronic Hepatitis B.
Zhou, L, Liu, X, Ren, F, Chen, Y, Zheng, S, Han, Y, Zhao, C, Duan, Z
Medical science monitor : international medical journal of experimental and clinical research. 2015;:2058-63
Abstract
BACKGROUND This study aimed to assess whether long-term entecavir monotherapy induces mitochondrial toxicity in patients with chronic hepatitis B (CHB). MATERIAL AND METHODS This was a prospective study in 34 antiviral treatment-naïve patients with CHB who received entecavir monotherapy and were followed up for 4 years. Blood samples were collected after 0, 2, 3, and 4 years of entecavir (ETC) monotherapy (ETC0, ETC2, ETC3, and ETC4, respectively). Mitochondrial DNA (mtDNA) contents were determined using real-time quantitative polymerase chain reaction (qRT-PCR) and mtDNA4977 depletions were detected using nested PCR. Levels of hepatitis B virus (HBV) DNA, alanine aminotransferase, alanine aminotransferase, hepatitis B e antigen (HBeAg), creatine kinase, urea nitrogen, and serum creatinine were recorded. RESULTS mtDNA contents at ETC0 (9.6±6.3) and ETC4 (10.3±6.2) were markedly higher than at ETC2 (0.8±0.5, P<0.01) and ETC3 (1.3±0.9, P<0.01), but there were no differences between ETC2 and ETC3 or between ETC0 and ETC4. MtDNA4977 depletion appeared in 79.4% cases at ETC2 and in 70.6% at ETC3, which were much higher than at ETC0 (32.4%, P<0.01) and ETC4 (8.8%, P<0.01), but there were no differences in mtDNA4977 depletion ratio between ETC2 and ETC3, or between ETC0 and ETC4. mtDNA content was negatively correlated to mtDNA4977 depletion (partial regression coefficient of -4.555, P<0.001, R2=0.315). mtDNA content was positively correlated with age (partial regression coefficient of 0.131, P=0.045). CONCLUSIONS Results suggest that during 4-year entecavir monotherapy for CHB, the mtDNA contents initially decreased and then increased, while the mtDNA4977 depletion rates first increased and then decreased.
-
9.
Bevacizumab plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as the second-line therapy for patients with metastatic colorectal cancer, a multicenter study.
Deng, T, Zhang, L, Liu, XJ, Xu, JM, Bai, YX, Wang, Y, Han, Y, Li, YH, Ba, Y
Medical oncology (Northwood, London, England). 2013;(4):752
Abstract
Poor prognosis is associated with patients with metastatic colorectal cancer. To seek effective methods, we examine the efficacy and safety of bevacizumab plus FOLFIRI as a second-line chemotherapy in Chinese patients with metastatic colorectal cancer (mCRC). A total of 55 patients with previous failure of oxaliplatin-based chemotherapy were included in this study, from October 2010 to February 2012. All patients received bevacizumab (5 mg/kg) plus FOLFIRI every other week until disease progression or intolerable toxicity occurred. The response rate was 31%, and the disease-controlled rate was 76.4%. The median progression-free survival was 6 months, and the median overall survival was 17 months. Adverse events (AEs) related to chemotherapy were mild to moderate. Only the incidence of grade 3-4 neutropenia reached to 25.5%. The incidence of AEs related to bevacizumab was low. These AEs included grade 3-4 toxicities of hypertension and proteinuria 5.4 and 3.6%, respectively. Bevacizumab plus FOLFIRI is an effective and safe regimen as a second-line treatment for patients with mCRC in China.
-
10.
Proteomic investigation of the interactome of FMNL1 in hematopoietic cells unveils a role in calcium-dependent membrane plasticity.
Han, Y, Yu, G, Sarioglu, H, Caballero-Martinez, A, Schlott, F, Ueffing, M, Haase, H, Peschel, C, Krackhardt, AM
Journal of proteomics. 2013;:72-82
Abstract
Formin-like 1 (FMNL1) is a formin-related protein highly expressed in hematopoietic cells and overexpressed in leukemias as well as diverse transformed cell lines. It has been described to play a role in diverse functions of hematopoietic cells such as phagocytosis of macrophages as well as polarization and cytotoxicity of T cells. However, the specific role of FMNL1 in these processes has not been clarified yet and regulation by interaction partners in primary hematopoietic cells has never been investigated. We performed a proteomic screen for investigation of the interactome of FMNL1 in primary hematopoietic cells resulting in the identification of a number of interaction partners. Bioinformatic analysis considering semantic similarity suggested the giant protein AHNAK1 to be an essential interaction partner of FMNL1. We confirmed AHNAK1 as a general binding partner for FMNL1 in diverse hematopoietic cells and demonstrate that the N-terminal part of FMNL1 binds to the C-terminus of AHNAK1. Moreover, we show that the constitutively activated form of FMNL1 (FMNL1γ) induces localization of AHNAK1 to the cell membrane. Finally, we provide evidence that overexpression or knock down of FMNL1 has an impact on the capacitative calcium influx after ionomycin-mediated activation of diverse cell lines and primary cells.