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The thermal management problems of traction drive systems for high-speed trains are of great importance for the operation reliability of high-speed trains. The thermal performance of transformer and traction rectifier are mainly affected by the aerodynamic performance of pantograph. Nine bowheads with different sawtooth structures on the lower surface are proposed and a CFD numerical model is built with Transition SST turbulence model. The influence of the number and height of sawteeth on the aerodynamic characteristics of the bowhead flow field are investigated. The results show that compared with the rectangular bowhead, the aerodynamic drag of the 5w3h-shaped bowhead is reduced by 8.6%, 8.7%, and 9.9% at train speeds of 250 km/h, 300 km/h, and 350 km/h, respectively. The promotion of aerodynamic performance of pantograph is beneficial to improve the thermal characteristics of traction drive systems for high-speed trains. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To confirm non‐inferiority and test potential superiority of capecitabine/cisplatin (XP) over 5‐fluorouracil (5‐FU)/cisplatin (FP) as first‐line treatment for advanced gastric cancer (AGC) in Chinese patients. Methods: In open‐label phase III ML17032 trial, AGC (stage IIIA–IV) patients with or without metastases were randomized 1:1 to receive cisplatin (80 mg/m2/day intravenous [IV] day 1) with either capecitabine (1000 mg/m2/day oral [PO] twice daily [BID], days 1–14; XP) or 5‐FU (800 mg/m2/day continuous IV days 1–5; FP) every 3 weeks. The primary objective was to confirm the non‐inferiority of XP over FP for progression‐free survival (PFS). Results: The intent‐to‐treat (ITT) population included 126 Chinese patients (XP–62, FP–64; 67.5% male, mean age 54.7 years). The primary analysis was performed on the per‐protocol (PP) population (105 patients; XP–51, FP–54; 65.7% male). Median PFS in the XP and FP groups was 7.2 and 4.5 months, respectively. The adjusted hazard ratio (HR) for PFS was 0.52 (95% confidence interval [CI]: 0.32–0.83, P = 0.006). Unadjusted HR for PFS in the ITT population was 0.63 (95% CI, 0.42–0.94, P = 0.022). The most frequent drug‐related grade 3/4 adverse events (AEs) were neutropenia (XP–20.7%, FP–17.7%) and gastrointestinal disorders (XP–19.0%, FP–19.4%). The overall incidence of grade 3/4 AEs (XP–43.1%, FP–46.8%), serious AEs (XP–1.7%, FP–3.2%), and AEs related to treatment discontinuation (XP–10.3%, FP–16.1%) were comparable. Conclusion: XP had a similar safety profile and may demonstrate superiority for PFS compared to FP as first‐line treatment of Chinese patients with AGC (NCT02563054). [ABSTRACT FROM AUTHOR]

Currently, the prognosis of neuroblastoma is poor, and new therapeutic strategies are needed. This study aimed at evaluating whether the administration sequence of bevacizumab and cyclophosphamide influenced the antitumor effects in a neuroblastoma model. Bevacizumab was administered at 5 mg/kg body weight weekly, alone or combined with cyclophosphamide, to treat a neuroblastoma xenograft in nude mice, and the tumor inhibition rates were compared. The functions of tumor vessels at different time points after bevacizumab administration were detected by Hoechst 33342 labeling. The antitumor effects of cyclophosphamide, administered concomitantly with bevacizumab or when vessel function was most improved post-bevacizumab administration, were compared. The tumor inhibition rates of the neuroblastoma xenograft treated with bevacizumab, cyclophosphamide, or both were 38.1, 44.0, and 56.0%, respectively ( P < 0.05). Bevacizumab reduced 64% of angiogenesis. Tumor vessel function was most improved 6 days after bevacizumab administration. The tumor inhibition rates in mice treated with cyclophosphamide, concomitantly with bevacizumab or 6 days after bevacizumab administration, were 55.9 and 66.8%, respectively ( P < 0.05). Bevacizumab can reduce neuroblastoma growth and has a synergistic effect when combined with cyclophosphamide in vivo. This synergistic effect is further enhanced when cyclophosphamide is administered after bevacizumab, when tumor vessel function is most improved. [ABSTRACT FROM AUTHOR]

Pirarubicin is an analog of doxorubicin. Few studies have compared the long-term outcomes of patients receiving pirarubicin-based THP-COP and doxorubicin-based CHOP in the treatment of non-Hodgkin's lymphoma (NHL). We retrospectively compared the efficacy and safety of these two regimens in 459 previously untreated aggressive NHL patients admitted to Sun Yat-Sen University Cancer Center from 1987 to 2003. For initial treatment, 205 patients received the THP-COP regimen, and 254 patients received the CHOP regimen. The patients' characteristics were well balanced. The groups did not differ in the complete remission rate (THP-COP, 57.1% vs. CHOP, 57.0%; P = 0.998) or response rate (THP-COP, 82.9% vs. CHOP, 81.5%; P = 0.691). At a median follow-up of 95.7 months, the 8-year survival rates were also similar (overall survival: THP-COP, 55.8% vs. CHOP, 56.7%; progression-free survival: THP-COP, 47.3% vs. CHOP, 43.5%; lymphoma-specific survival: THP-COP, 51.2% vs. CHOP, 48.5%). The THP-COP group had fewer cases of alopecia (P < 0.001) and gastrointestinal toxicities (P = 0.015). A tendency toward decreased arrhythmia (P = 0.075), especially in elderly patients (P = 0.030), was found. In combination chemotherapy for aggressive NHL, pirarubicin has comparable efficacy to doxorubicin and has a lower incidence of alopecia, gastrointestinal toxicities, and arrhythmia. Further studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy. Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival (DFS) and overall survival (OS) of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin’s Lymphoma (NHL) remains to be defined. This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively. Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old (range 18 to 75); 50 patients (92.6%) scored 0–1 for the ECOG performance status; for second-line international prognostic index (sIPI), 21 (38.9%) scored 0–1, 30 (55.6%) scored 2 to 3, and 3 (5.6%) scored 4–5; 40 cases were diffuse large B-cell lymphoma (DLBCL), accounting for 74.1% of all subtypes. Rituximab was administered intravenously at a dose of 375 mg/m2 at the day before each chemotherapy cycle. The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND. Of the 54 patients, 49 received retuximab-containing salvage regimens. The objective response rate of the 45 evaluable cases was 68.8%, with a complete remission (CR) rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation. The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months (range 2–86 months); 5 patients were lost, 24 were dead (23 died of lymphoma, and 1 died of severe hepatitis), the other patients remained alive. The median survival time was 32 months (range 2–86 months, 95% confidential interval 16–48 months). The 1-, 2-and 3-year OS rates were 70.6%, 53.6% and 41.5%, respectively. The median TTP was 6 months (range 0–52 months). The median PFS was 10 months (range 0–47 months, 95% CI 0–26 months). The 1-and 2-year PFS were 49.3% and 41.3%. Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and tolerability of letrozole with aminoglutethimide (AG) in postmenopausal women with advanced breast cancer. Methods: The multicenter, randomized controlled clinical trial was conducted in 113 patients. They randomly received letrozole 2.5 mg once daily (letrozole group) or AG 250 mg 4 times daily (AG group) with hydrocortisone. Results: The OR in letrozole group was 23.73% (2 cases of CR and 12 cases of PR, ITT OR was 21.88%), which was higher than in AG group (the OR 11.11%, 1 CASE of CR and 5 cases of PR, ITT 10.17%), but there was no statistically significant difference (P>0.05). Adverse events (AE) and the treatment related AE (RAE) in letrozole group (n=59) was 18.54% and 13.56% respectively, significantly lower than those (42.11% and 33.33% respectively) in AG group (n=57, P=0.002). Conclusion: The OR of letrozole in the treatment of postmenopausal advanced breast cancer positive or unknown for hormonal receptor is 23.73%, showing no significant difference to that of AG. The AE of letrozole are significantly less than AG. [ABSTRACT FROM AUTHOR]

Introduction: Phosphatidylinositol 3-kinase (PI3K) pathway deregulation (that is PIK3CA mutations and/or phosphatase and tensin homolog (PTEN) loss) has been shown to enhance breast cancer cell survival and confer resistance to chemotherapeutic agents. We studied the prognostic and predictive value of PIK3CA mutations and PTEN low in patients receiving paclitaxel alone or in combination with lapatinib.Methods: Immunohistochemistry and mutation analyses were used to evaluate PTEN and PIK3CA, respectively. Kaplan-Meier analysis with log-rank tests, logistic regression and Cox models were used in analyses of these biomarkers with efficacy endpoints.Results: In the overall population, PIK3CA mutations were associated with poorer overall survival (OS) (hazard ratio (HR) = 1.87; 95% confidence interval (CI): 1.22, 2.88; P = 0.001). PTEN expression was not associated with OS (P = 0.474). In the PIK3CA wild-type subgroup, lapatinib plus paclitaxel reduced risk of progression compared with paclitaxel alone (HR = 0.44; 95% CI: 0.28, 0.69; P <0.0001); progression-free survival (PFS) was not significantly improved within the PIK3CA mutation subgroup (P = 0.179). In the PTEN low group, OS was improved with addition of lapatinib (P = 0.039). In both PTEN subgroups, addition of lapatinib was associated with improvements in PFS (P <0.050). PIK3CA and PTEN were not predictive of treatment based on interaction tests (P >0.05).Conclusions: PTEN was neither a significant prognostic nor predictive factor. PIK3CA mutations were an adverse prognostic factor for survival but not predictive for lapatinib benefit.Trial Registration: ClinicalTrials.gov NCT00281658 (registered 23 January 2006). [ABSTRACT FROM AUTHOR]

Background: It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(gamma-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound.Methods: 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres.Results: 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 microg/L vs. 17047.3 microg/L), and greater distribution volume (VD, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05).Conclusion: In our model system, 5-FU/PEG-PBLG nanoparticles changed the pharmacokinetic behavior of 5-FU, thus increasing its anticancer activity. 5-Fluorouracil loaded nanoparticles have potential as a novel anticancer drug that may have useful clinical applications. [ABSTRACT FROM AUTHOR]