Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis.

The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA) leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE), and flow cytometry methods. Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP). There was also no translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. Our findings provide the molecular mechanisms by which Tan IIA can be used to treat psoriasis and support the traditional use of Salvia miltiorrhiza Bungee (Labiatae) for psoriasis and related skin diseases.

Distinct EphB4-mediated mechanisms of apoptotic and resistance to dasatinib in human chronic myeloid leukemia and K562 cell lines.

OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (108) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models. RESULT: The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67µg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1µg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30µg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01). CONCLUSIONS: The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1/PTEN/MCL-1 signaling.

Percutaneous coronary intervention for acute myocardial infarction with mitral regurgitation.

Ischemic mitral regurgitation (IMR) is a common complication of acute myocardial infarction (AMI). Current evidences suggest that revascularization of the culprit vessels with percutaneous coronary artery intervention (PCI) or coronary artery bypass grafting can be beneficial for relieving IMR. A 2.5-year follow-up data of a 61-year-old male patient with ST-segment elevation AMI complicated with IMR showed that mitral regurgitation area increased five days after PCI, and decreased to lower steady level three months after PCI. This finding suggest that three months after PCI might be a suitable time point for evaluating the possibility of IMR recovery and the necessity of surgical intervention of the mitral valve for AMI patient.

Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome.

OBJECTIVE: The open-label, prospective, observational study aimed to evaluate whether decitabine (DAC) plus thalidomide versus DAC monotherapy improved progression-free (PFS), overall survival (OS) and acute myeloid leukemia-free survival (AML-FS) for risk-tailored elderly patients with myelodysplastic syndromes (MDS). METHOD: Enrolled 107 patients (age: 65-82 years) received DAC (52/107) or DAC plus thalidomide (55/107) therapy for MDS. RESULTS: 35/52 patients (67.3%) with DAC therapy reached overall response (OR), compared with 36/55 patients (65.5%) in DAC+thalidomide regimen (P>0.05). DAC+thalidomide administered did not gain more profits of PFS and OS than DAC monotherapy. Risk-tailored analysis showed that DAC+thalidomide therapy did not enhance PFS (48.9% versus 42.8%, P>0.05) and OS (78.6% versus 71.2%, P>0.05) when compared with simple DAC regimen. Nevertheless, DAC+thalidomide markedly improved OS over DAC monotherapy (50.6% versus 40.2%, P<0.05) in high risk profile. Meanwhile, low risk group was superior to high risk group in AML-FS (57.2% versus 21.3%, P<0.01), but DAC+thalidomide still did not prolong 2-year AML-FS when compared with DAC (32.4% versus 27.8%, P<0.05). Moreover, thalidomide had a favorable toxicity profile as a single agent. In comparison with DAC monotherapy, the DAC+thalidomide regimen was relatively well tolerated. There was no severe non-hematological toxicity appearing in elderly patients with MDS. CONCLUSIONS: The study demonstrated that DAC+thalidomide improved 2-year OS for high risk patients. Thalidomide's proven activity and low toxicity profile made it an alternative treatment option for risk-tailored elderly patients with MDS.

Homoharringtonine contributes to imatinib sensitivity by blocking the EphB4/RhoA pathway in chronic myeloid leukemia cell lines.

The purpose was to investigate the role of EphB4 in imatinib (IM) resistance and the mechanism responsible for homoharringtonine (HHT) contributing to imatinib sensitivity for a chronic myeloid leukemia (CML) cell lines. We established cell lines from a patient with CML at the time of first diagnosis and relapsed phase and designated them as NPhA1 and NPhA2, respectively. Stable underexpressing EphB4 cells (NPhA2-sh) were obtained. The activated signal proteins in cells were tested by Western blot. The EphB4 was overexpressed in IM-resistant NPhA2 in comparison with the NPhA1 cell line, but the expression of EphB4 mRNA and protein significantly decreased in knockdown NPhA2-EphB4-sh cells compared with NPhA2 and NPhA1 (P < 0.001) cell lines. NPhA2-EphB4-sh cells were sensitive to IM (IC50 0.93 mg/L), and NPhA2 showed IM resistance (IC50 5.45 mg/L) (P < 0.001). Meanwhile, phospho-Rac1/cdc42 was significantly increased in NPhA2 cells compared to NPhA2-EphB4-sh (P < 0.001). The apoptosis rate reached 58.71 ± 2.39 % with NPhA2 cells incubated with HHT + IM, which was higher than NPhA2 cells incubated with IM alone (P = 0.002). IC50 of NPhA2 cells incubated with IM was 5.45 mg/L. However, co-stimulation with HHT + IM decreased the IC50 of NPhA2 cells from 5.45 to 1.17 mg/L (P < 0.001). Furthermore, HHT blocked the expressions of EphB4/RhoA, but did not down-regulate the phospho-MEK/ERK in NPhA2 cells. The overexpression of EphB4 contributed to IM resistance in CML line cells. EphB4/RhoA may be a new marker of IM resistance. HHT + IM gained more treatment advantages than IM alone by blocking EphB4/RhoA pathways in CML cell lines.

A prospective, observational study of added medium-dose cytosine arabinoside versus As2O3 for elderly patients with acute promyelocytic leukemia.

This open-label, prospective, observational study aimed to evaluate disease-free survival (DFS), overall survival (OS), PML-RARα polymerase chain reaction (PCR) monitoring and safety in elderly patients with de novo acute promyelocytic leukemia (APL) who were treated with either arsenic trioxide (As2O3) or medium-dose cytosine arabinoside (MiDAC) as frontline consolidation regimens. A total of 167 patients (age≥65 years old) received all-trans retinoic acid + daunorubicin as induction therapy. Of these patients, 22 died before attaining complete remission; the remaining 145 subjects received MiDAC- or As2O3-based consolidation therapy. As2O3 was superior to MiDAC for improving DFS and OS. This benefit appeared to result from the longer 5-year DFS (92.0 vs. 69.1%, P<0.01) and OS (94.5 vs. 79.7%, P<0.05) of As2O3 compared to MiDAC. PCR monitoring demonstrated that As2O3 promoted a lower positive rate than MiDAC (21.7 vs. 4.5%, P<0.05), but this treatment had no advantage for maintaining a low positive rate in the high-risk group. The most common life-threatening adverse drug effects in patients with MiDAC were platelet counts<25×10(9)/L (85.7%), leukocyte counts<1.0×10(9)/L (81.4%) and severe infection (84.3%). In contrast, the As2O3 regimen rarely caused leukocyte counts<1.0×10(9)/L (22.7%, P<0.01), platelet counts<25×10(9)/L (37.3%, P<0.01) or severe infection (21.3%, P<0.01). These data confirm that MiDAC should not be added during the initial consolidation of patients with APL because this treatment is far less effective, particularly in patients with a low-risk profile, and far more toxic than As2O3.

Interferon α-2b gains high sustained response therapy for advanced essential thrombocythemia and polycythemia vera with JAK2V617F positive mutation.

OBJECTIVE: This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN α-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation. METHOD: A total of 123 ET patients received IFNα-2b therapy with JAK2V617F positive or negative mutation; and 136 PV patients with JAK2V617F(+) received IFNα-2b or hydroxyurea (HU) therapy according to random number assignment (ages 18-65 years old). RESULT: ET patients receiving IFN α-2b with JAK2V617F(+) had a greater advantage in overall hematologic response (OHR) than JAK2V617F(-) (83.3% versus 61.4%, P<0.01). For PV patients with JAK2V617F(+), IFN had no OHR superiority to HU (70.3% versus 70.8%, P>0.05), but which gained a greater satisfactory molecular response than HU (54.7% versus 19.4%, P<0.01). IFN significantly decreased the phlebotomy rate, which was better than HU for MPDs patients with OHR than HU (3.6% versus 65.7%, P<0.01). Furthermore, ET patients with JAK2V617F(+) demonstrated a definite advantage over JAK2V617F(-) in five-year PFS (75.9% versus 47.6%, P<0.05). For PV patients with JAK2V617F(+), IFN α-2b was superior to HU in five-year PFS (66.3% versus 46.7%, P<0.01). Moreover, IFN α-2b also contributed to improved vasomotor symptoms in MPDs, and especially significantly decreased the incidence of distal paresthesias (14.1% versus 37.5%) and erythromelalgia (9.4% versus 29.2%) better than HU (P<0.01). Meanwhile, IFN did not observe the severe hematological adverse events in patients with PV or ET. CONCLUSION: The data confirmed that IFN α-2b benefited the patients with ET or PV, particularly for JAK2V617F(+) mutation.

How to determine post-FCR therapy for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia, maintenance rituximab or observation.

The open-label, prospective, observational study aimed to evaluate whether the addition of maintenance rituximab (MR) improved progression-free survival (PFS) and overall survival (OS), after fludarabine, cyclophosphamide, and rituximab (FCR) for cytogenetic risk-tailored elderly patients with chronic lymphocytic leukemia (CLL). Enrolled 201 patients (ages 65-84 years) who received FCR and gained an overall response. One hundred and four of 201 patients were in the observation (OBS) arm while 97/201 patients continued to receive MR therapy. After FCR, no more benefits were provided by MR versus OBS in cytogenetic better intermediate-risk cohort. PFS at 10 years reached 68.6 versus 58.1 % (P > 0.05). Ten-year OS was 81.8 versus 74.6 % (P > 0.05). However, the improvement of PFS and OS were as dramatic as the improvements of being MR treating versus OBS mainly in the poor-risk cohort. PFS at 10 years reached 57.1 versus 22.7 % (P < 0.01), and 10-year OS was 71.2 versus 41.7 % (P < 0.01). Compared with OBS, no severe hematologic adverse events (AEs) (Grades 3-4) appeared in patients with MR; only some mild non-hematologic AEs incurred (nausea-vomiting 0.96 %, allergy 1.9 % and infection 1.9 %) during the maintenance treatment. The study showed that MR improved 10-year RFS and OS for cytogenetic poor-risk patients with CLL.

Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with acute myeloid leukemia.

The open-label, prospective study aimed to evaluate the efficacy and safety for standard intensive chemotherapy compared with attenuated therapy in elderly patients with acute myeloid leukemia (AML). A total of 297 patients between 65 and 82 years were enrolled in the study. The 141 patients received standard-dose therapy (daunorubicin 45 mg/m(2) × 3 days with cytarabine 100 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of high-dose cytarabine 1.5 g/m(2) × 4 days), and the attenuated treatment (daunorubicin 30 mg/m(2) × 3 days with cytarabine 75 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of attenuated high-dose Ara-C 1.0 g/m(2) × 3 days) was administered to the remaining 156 patients, based on a random number assigned. Total 168 patients (56.6%) achieved complete remission with an incomplete blood recovery (CR)/CRi. No significant differences were observed between the two treatments (P = 0.60). Attenuated chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared to standard-dose therapy; 5-year OS values for these two groups were 39 and 24 months, respectively (P < 0.001), and the PFS values for these two groups were 35 versus 23 months (P < 0.001). In addition, the attenuated treatment with a poor risk profile overcame the negative impact and yielded OS and PFS values similar to those of the standard-dose chemotherapy with a better-to-intermediate risk profile. Five-year OS values for these two groups were 28 versus 28 months (P = 0.89), and the 5-year PFS values were 27 and 28 months, respectively (P = 0.89). The most common adverse drug effect for chemotherapy was agranulocytosis (98.3%). There was a significant difference in early mortality between the attenuated and standard-dose treatment groups (0.64% vs. 7.1%, respectively, P < 0.01). Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with AML.

How to determine bortezomib-based regimen for elderly patients with multiple myeloma: PAD versus CBd, an observational study.

BACKGROUND: This was an open-label, observational, prospective assessment. We conducted an analysis of the impact of bortezomib-based therapy (PAD: bortezomib, doxorubicin, high-dose dexamethasone vs. CBd: cyclophosphamide bortezomib, low-dose dexamethasone) on the survival rates and adverse events in elderly patients with newly diagnosed multiple myeloma (MM). METHODS: Out of 303 patients, 128 received the PAD regimen and the other 175 patients received the CBd induction therapy (age 65-89 years). Baseline patient characteristics between the two cohorts were balanced in age (P = 0.69), international staging system (ISS) prognostic stages (P = 0.90), serum calcium (P = 0.70), and serum creatinine (P = 0.52). RESULTS: Overall response (OS) after the induction chemotherapy was achieved in 214 of 303 patients (70.6 %), with no significant differences observed between the two treatment groups (71.9 vs. 69.7 %, P = 0.68). Patients with ISS stage 2 reached the same 5-year OS advantages compared to patients with ISS stage 1, because they received bortezomib-based PAD or CBd treatments. Patients receiving CBd protocol gained similar satisfactory progression-free survival (PFS) results when compared to the PAD regimen group: PFS at 5 years reached 58.2 versus 58.9 % (P = 0.85). Five-year OS in the CBd arm had significant advantages compared to the PAD group, 79.9 versus 49.9 % (P < 0.05). The overall safety profiles showed that 26 of 128 (20.3 %) patients died in the PAD arm, while 13 of 175 patients died (7.4 %) in the CBd group (P < 0.01). Similarly, the PAD arm had a higher serious infection rate than that of the CBd arm (39.2 vs. 13.1 %, P < 0.01). CONCLUSIONS: Bortezomib benefits elderly patients with newly diagnosed MM; they achieve satisfactory treatment responses and survival advantages. Further, patients treated with CBd have superior treatment advantages, with a predictable safety profile, when compared to the PAD regimen.

Sclederma of Poria cocos exerts its diuretic effect via suppression of renal aquaporin-2 expression in rats with chronic heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Sclederma of Poria cocos (Hoelen) has been used as a diuretic in traditional Asian medicine. However, the underlying mechanism by which Sclederma of Poria cocos (hoelen) exerts its diuretic effect has not been well identified. The aim of the present study was to evaluate the effects of Sclederma of Poria cocos (hoelen) in rats with chronic heart failure (CHF) induced by acute myocardial infarction and to investigate the underlying mechanisms. MATERIALS AND METHODS: An aqueous extract of Sclederma of Poria cocos (hoelen) (2.4 g/kg/d, 1.2 g/kg/d or 0.6 g/kg/d) or furosemide (20 mg/kg/d) was administered orally to male Sprague-Dawley rats starting on the day of coronary ligation. The urine output of all rats was quantified and collected every day for 1 or 4 weeks. The expression of aquaporin-2 (AQP2) was examined after treatment for 1 or 4 weeks. RESULTS: Urinary output increased significantly and urinary osmolality decreased after oral administration of Sclederma of Poria cocos (hoelen) for both 1 and 4 weeks. Sclederma of Poria cocos (hoelen) caused less electrolyte disorder than furosemide. Furthermore, Sclederma of Poria cocos (hoelen) reduced the levels of plasma BNP in CHF rats, whereas furosemide had no effect. Importantly, both mRNA and protein expression of AQP2 were down-regulated and urinary excretion of AQP2 was decreased after administration of Sclederma of Poria cocos (hoelen) to CHF rats. Similarly, Sclederma of Poria cocos (hoelen) reduced plasma arginine vasopressin (AVP) level and down-regulated vasopressin type 2 receptor (V2R) mRNA expression. CONCLUSIONS: Sclederma of Poria cocos (hoelen) exerts its diuretic effect and improves cardiac function in CHF rats via the AVP-V2R-AQP2 axis.

Excretion of urinary orosomucoid 1 protein is elevated in patients with chronic heart failure.

Easily screening markers for early detection of chronic heart failure (CHF) are lacking. We identified twenty differently expressed proteins including orosomucoid 1(ORM1) in urine between patients with CHF and normal controls by proteomic methods. Bioinformatics analyses suggested ORM1 could be used for further analysis. After verification by western blotting, the urinary levels of ORM1 were quantified with enzyme-linked immunosorbent assay (ELISA) by correcting for creatinine expression. The ORM1-Cr was significantly elevated in CHF patients than normal controls (6498.83 ± 4300.21 versus 2102.26 ± 1069.24 ng/mg). Furthermore, a Spearman analysis indicated that the urinary ORM1 levels had a high positive correlation with the classification of CHF, and the multivariate analysis suggested that the urinary ORM1 content was associated with the plasma amino-terminal pro- brain natriuretic peptide (NT-proBNP) (OR: 2.106, 95% CI: 1.213-3.524, P = 0.002) and the New York Heart Association (NYHA) classification (OR: 3.019, 95% CI: 1.329-4.721, P<0.001). In addition, receiving operating curve (ROC) analyses suggested that an optimum cut-off value of 2484.98 ng/mg with 90.91% sensitivity and 85.48% specificity, respectively, could be used for the diagnosis of CHF. To sum up, our findings indicate that ORM1 could be a potential novel urinary biomarker for the early detection of CHF.

High-dose homoharringtonine versus standard-dose daunorubicin is effective and safe as induction and post-induction chemotherapy for elderly patients with acute myeloid leukemia: a multicenter experience from China.

The purpose of the study was to compare the antitumor efficacy and safety profile of high-dose homoharringtonine as induction and post-induction therapy compared to either standard-dose homoharringtonine or daunorubicin in elderly patients with newly diagnosed acute myeloid leukemia. A total of 254 patients, age range 60-77 years received induction and post-induction therapy containing daunorubicin, standard-dose homoharringtonine, or high-dose homoharringtonine. After one course of induction therapy, the overall complete remission rate was similar between treatment arms (58.7%, P = .92). Among 161 patients with acute myeloid leukemia (non-M5 subtype), estimated median overall survival was 39, 29, and 37 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .53). In the 93 patients with acute myeloid leukemia-M5 subtype, there was a significant difference in estimated median overall survival: 24, 24, and 52 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .003). There was no significant difference in drug-related adverse events between treatment arms. High-dose homoharringtonine does not clearly increase the complete remission rate of elderly patients with acute myeloid leukemia. However, in the subset of elderly patients with acute monocytic leukemia, high-dose homoharringtonine as a first-line regimen prolonged overall survival with minimal toxicity.

How to determine post-RCHOP therapy for risk-tailored adult patients with diffuse large B-cell lymphoma, addition of maintenance rituximab or observation: multicenter experience.

BACKGROUND: In international prognostic index (IPI) risk-tailored adult patients with diffuse large B-cell lymphoma (DLBCL), it is still unclear whether the addition of maintenance rituximab (MR) improves progression-free (PFS) and overall survival (OS), after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. METHODS: In our study, 207 patients (age: 21-59 years) received six 14-day cycles of RCHOP and gained overall response. After RCHOP, 98 patients were enrolled in the observation (OBS) arm. 109 patients continued to receive MR therapy. RESULTS: In IPI risk <2 profile, PFS at 5 years reached 72.9% (MR arm) versus 56% (OBS arm) (P = 0.033). In IPI risk ≥2 profile, PFS estimation at 5 years was 44.9% (MR arm) versus 33.5% (OBS arm) (P = 0.006). It is noteworthy that patients with IPI ≥2 who received MR achieved PFS similar to that for patients in the OBS arm with the IPI <2, 44.9% versus 56% (P = 0.97). In patients with an IPI <2, OS at 5 years was 83.2% (MR arm) versus 81.2% (OBS arm) (P = 0.708). In patients with an IPI ≥2, 5-year OS estimation was 44.6% (MR arm) versus 40.5% (OBS arm) (P = 0.067). Subgroup analysis of patients with an IPI ≥3 risk profile shows a survival benefit for patients receiving MR. OS at 5 years was 62% (MR arm) versus 49% (OBS arm), (P = 0.033). CONCLUSIONS: In conclusion, maintenance rituximab after RCHOP improves progression-free survival. In addition, overall survival is improved for patients with an IPI ≥3 risk profile receiving MR.

The early addition of arsenic trioxide versus high-dose arabinoside is more effective and safe as consolidation chemotherapy for risk-tailored patients with acute promyelocytic leukemia: multicenter experience.

The purpose of the study was to evaluate event-free survival (EFS), overall survival (OS) and safety for early addition of arsenic trioxide (As(2)O(3)) as frontline consolidation therapy compared to high-dose arabinoside (HiDAC) in adult patients with de novo acute promyelocytic leukemia (APL). 271 patients (aged 17-65 years) received consolidation therapy containing As(2)O(3) (two 21-day courses) or HiDAC regimen. EFS at 5 years was 75% versus 54% (P < 0.001), and OS at 5 years was 83% versus 71% (P = 0.002) in As(2)O(3) and HiDAC treatment arms. 139 patients treated with As(2)O(3), EFS at 5 years reached 79% versus 56% (P = 0.014), but OS at 5 years was 77% versus 84% (P = 0.32) in low-risk (WBC ≤ 10 × 10(9)/L) and high-risk (WBC > 10 × 10(9)/L) cohorts. Further, patients treated with As(2)O(3) rarely incurred agranulocytosis (1.4%, P < 0.001), or severe infection (0.7%, P < 0.001). It is still very well tolerated compared to HiDAC. We confirmed that As(2)O(3) as a first-line consolidation regimen provided significant benefits of OS to patients with APL. The As(2)O(3) regimen made low-risk patients gain more EFS benefits than high-risk group. The high-risk cohort receiving As(2)O(3) overcame the negative impact, yielding OS similar to that for with the low-risk patients treated with As(2)O(3).

Analysis of efficacy and cost-effectiveness of high-dose arabinoside versus daunorubicin chemotherapy in older adult patients with acute myeloid leukemia by cytogenetic risk profile: retrospective review from China.

High-dose arabinoside (HiDAC) and daunorubicin (DNR)-based chemotherapy are the primary consolidation treatment options for older adults (50-60 years old) with acute myeloid leukemia in China. We analyzed the event-free survival (EFS) and hospital treatment charges of older adult patients with different cytogenetic risk profiles. In patients with a better/intermediate risk profile, the average total treatment cost of HiDAC was similar to that of DNR (P = 0.11). A 5-year follow-up of patients with better/intermediate cytogenetic risk profiles revealed that the median EFS of patients who received HiDAC was significantly longer than for patients who received the DNR-based regimen (27 vs. 20 months, P = 0.03). Average cost per year of life saved was 18,746.84 USD for HiDAC, compared to 32,733.37 USD for DNR. In contrast, for patients with a poor cytogenetic risk profile, the average total treatment cost for HiDAC was higher than for DNR (P < 0.005). In addition, the median EFS in the HiDAC protocol group was significantly lower than in the DNR group (11 vs. 20 months, P = 0.003). Meanwhile, in this risk group, the average cost per year of life saved was 103,237.70 USD compared to 32,277.93 USD, respectively, in the HiDAC and DNR regimens. We conclude that HiDAC is a more efficacious and cost-effective consolidation treatment regimen in the better/intermediate risk group, while the DNR-based regimen is more cost-effective in the poor risk group.

Characteristics of ATP-activated current in nodose ganglion neurons of rats.

The characteristics of ATP-activated currents (I(ATP)) in rat nodose ganglion (NG) neurons have not been fully clarified. Especially, the correlation between I(ATP) phenotype and P2X receptor subunit genotype in rat NG neuron is not clear. By whole-cell patch-clamp and single cell immunocytochemical techniques, we explored the characteristics of the I(ATP) phenotype and its correlation with P2X receptor subunits in acutely isolated NG neuron of rats. The results indicated that I(ATP) of NG neurons can be classified into four types: F type (fast type, 8.1%), I type (intermediate type, 14.8%), S type (slowing type, 37.0%) and vS type (very slowing type, 21.5%). The single immunocytochemical studies have demonstrated that F type cells express P2X1 and P2X3 subunits, I type cells P2X1, P2X3 and P2X4 subunits, S type cells P2X1, P2X2 and P2X3 subunits and vS type cells P2X2, P2X3 and P2X4 subunits. The results reveal that there are four types of I(ATP) in NG neurons, differential expression of distinct P2X subunits may underlie the I(ATP) phenotype.