Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia.

BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. MATERIAL AND METHODS 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment. Overall survival was analyzed by Kaplan-Meier method. RESULTS No differences were observed between patients and controls regarding the distribution frequency of genotype and alleles of rs1544105. Patients carrying AA genotype had a significantly higher plasma concentration of MTX after 24 h than those carrying GG or GA (P<0.05) and no differences were found after 44 h. Kaplan-Meier survival analysis showed a longer median survival time in patients with AA than other genotypes with significant difference in overall survival. CONCLUSIONS Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX.

Effect and mechanism of miR-34a on proliferation, apoptosis and invasion of laryngeal carcinoma cells.

OBJECTIVE: To discuss the effect and mechanism of miR-34a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. METHODS: The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34a mimics and miR-34a NC. The MTT, colony-forming assay, Hoechst staining and AnnexinV-PI double staining flow cytometry were employed to detect the effect of miR-34a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RT-PCR assay to defect the effect of miR-34a mimics on the expression of survivin and Ki-67 mRNA in laryngeal squamous carcinoma Hep2 cells. RESULTS: Compared with miR-34a NC group, the cell viability in miR-34 mimics group was significantly decreased (P < 0.01), the cell apoptosis rate was significantly increased (P < 0.01), the abilities of cell migration and invasion were significantly reduced (P < 0.01) and the expression of survivin and Ki-67 mRNA was significantly decreased (P < 0.01). CONCLUSIONS: The increased expression of miR-34a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67.

Correlation of survivin, p53 and Ki-67 in laryngeal cancer Hep-2 cell proliferation and invasion.

OBJECTIVE: To investigate the mechanism of survivin, p53 and Ki-67 on Hep-2 human laryngeal cancer endothelial cell proliferation and invasion. METHODS: Laryngeal squamous cell carcinoma and paracancerous normal tissues were collected, total RNA was extracted from tissues, survivin, p53 and Ki-67 gene mRNA expression levels in laryngeal cancer and the adjacent tissues were detected by Real-time PCR. Human laryngeal cancer Hep-2 epithelial cells were selected, survivin gene was overexpressed, and cell proliferation was detected by MTT. p53 and Ki-67 gene expression changes in overexpressed survivin gene were detected by Western blot. Changes in Hep-2 cell invasive ability were studied when survivin was overexpressed as detected by Transwell invasion assay. RESULTS: In the adjacent tissues, survivin, p53 and Ki-67 gene relative expression levels were 1.72 ± 0.9, 13.7 ± 5.7 and 5.7 ± 1.3, respectively; while in cancer tissues, gene relative expression levels were 53.7 ± 8.3, 66.7 ± 5.2 and 61.0 ± 3.1, respectively, which was significantly increased. As detected by MTT, relative cell survival rate within 12 h of survivin overexpression were: load control group (88.5 ± 1.6)%; overexpressed group (90.3 ± 1.9)%. Transwell invasion assay results indicated that overexpressed survivin could significantly increase the relative survival rate of cells. CONCLUSIONS: Expressions of p53, Ki67 and survivin are increased in cancer; and there is a positive correlation between survivin, p53 and Ki67 expressions in laryngeal carcinoma.

[Influence of improved Kennard/Stone algorithm on the calibration transfer in near-infrared spectroscopy].

The Kennard/Stone(K/S) algorithm is adopted to select the transfer set samples in the near infrared analysis calibration transfer by calculating the Euclidean distance of the spectrum of the samples. In order to get a best expression of the comparability of the samples and select the best samples for calibration transfer, piecewise direct standardization (PDS) algorithm was investigated for resolving calibration transfer of near-infrared spectra of mixed amine, then the Euclidean distance and the Mahalanobis distance were applied to calculate the comparability of the spectra of the samples and the standard error of prediction (SEP) was used to evaluate them. The combination of spectral difference and property difference was introduced to estimate the effect of individual spectral difference and property difference. The experimental results showed that the Mahalanobis distance was better than the Euclidean distance in PDS and the combination of spectral difference and property difference was more effective in expressing the comparability of the samples.

[Testosterone therapy improves cardiac function of male rats with right heart failure].

OBJECTIVE: Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats. METHODS: Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations. RESULTS: The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups. CONCLUSION: Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

[Effect of total saponins of Panaxginseng on bax and bcl-xl gene expression in HL-60 cells].

The aim of this study was to investigate the effect of the total saponins of Panaxginseng (TSPG) on cells expression of apoptosis-related genes bax and bcl-xl in HL-60 cells and its mechanism inducing apoptosis of HL-60 cells. The morphology of HL-60 cells was observed under normal and fluorescence microscopes; the percentage of apoptotic HL-60 cells was assayed by flow cytometry and the DNA ladder was observed by DNA agarose gel electrophoresis; the expression changes of bax and bcl-xl mRNAs were detected by RT-PCR after HL-60 cells were treated with TSPG at final concentrations of 0, 100, 200, 400, 800 and 1600 microg/ml for 48 hours. The results showed that the percentage of apoptotic HL-60 cells went up as the dose increased, the typical apoptotic cell morphology and the appearance of apoptotic DNA ladder could be observed when treated with 0 - 400 microg/ml TSPG for 48 hours. At the same time and same range of concentration, the expression of bax mRNA increased and the bcl-xl expression decreased gradually. When higher than 400 microg/ml of TSPG was used, cell necrosis appeared and the percentage of apoptotic HL-60 cells even decreased. It is concluded that the apoptosis or necrosis in HL-60 cells can be induced by TSPG at certain range of concentration, and the percentage of apoptosis is dose-dependent. The effect on up-regulation of bax mRNA and down-regulation of bcl-xl mRNA probably play an important role in apoptosis of HL-60 cells induced by TSPG.