Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non–Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor Receptor Mutation in Either Exon 19 or 21

Background:Gefitinib and erlotinib, small-molecule kinase inhibitors that block epidermal growth factor receptor (EGFR) signaling, have demonstrated a dramatic response rate and prolonged progression-free survival (PFS) in patients harboring an activating EGFR mutation. We compared the clinical outcomes in gefitinib- and erlotinib-treated patients harboring EGFR mutations who had recurrent or metastatic non–small-cell lung cancer (NSCLC).Methods:A total of 375 patients with recurrent or metastatic stage IIIB/IV NSCLC, who had either exon 19 deletion or the L858R mutation in exon 21, and had received either gefitinib (n = 228) or erlotinib (n = 147), were included in the study. A matched-pair case-control study design was implemented in the analysis, where 121 pairs of gefitinib-treated and erlotinib-treated patients were matched according to sex, smoking history, Eastern Cooperative Oncology Group performance status, and types of EGFR mutation.Results:The median age of all patients was 58 years (range, 30–84), and more than half of patients had never been smokers (63.6%). Most patients had adenocarcinoma (98.3%) and good Eastern Cooperative Oncology Group performance status (0, 1) (90.9%). The median number of cycles of EGFR tyrosine kinase inhibitor (TKI) treatment was 12.7 in the gefitinib group and 10.8 in the erlotinib group. Of the 242 patients, 63 (26%) received EGFR TKI as first-line therapy. The overall response rates and disease control rates in the gefitinib- or erlotinib-treated groups were 76.9% versus 74.4% (p = 0.575) and 90.1% versus 86.8%, respectively (p = 0.305). There was no statistically significant difference with regard to PFS (median, 11.7 versus 9.6; p = 0.056) between the gefitinib- and erlotinib-treated groups. For patients receiving EGFR TKI as the first-line treatment, there was no significant difference between the two treatment groups in overall response rates (76.7% and 90.0%) (p = 0.431) and median PFS (11.7 versus 14.5 months) (p = 0.507).Conclusion:In NSCLC patients harboring EGFR mutation, treatment with gefitinib and erlotinib resulted in similar effectiveness

Carbonyl‐ β ‐Cyclodextrin as a Novel Binder for Sulfur Composite Cathodes in Rechargeable Lithium Batteries

As one of the essential components in electrodes, the binder affects the performance of a rechargeable battery. By modifying β ‐cyclodextrin ( β ‐CD), an appropriate binder for sulfur composite cathodes is identified. Through a partial oxidation reaction in H 2 O 2 solution, β ‐CD is successfully modified to carbonyl‐ β ‐cyclodextrin (C‐ β ‐CD), which exhibits a water solubility ca. 100 times that of β ‐CD at room temperature. C‐ β ‐CD possesses the typical properties of an aqueous binder: strong bonding strength, high solubility in water, moderate viscosity, and wide electrochemical windows. Sulfur composite cathodes with C‐ β ‐CD as the binder demonstrate a high reversible capacity of 694.2 mA h g (composite) −1 and 1542.7 mA h g (sulfur) −1 , with a sulfur utilization approaching 92.2%. The discharge capacity remains at 1456 mA h g (sulfur) −1 after 50 cycles, which is much higher than that of the cathode with unmodified β ‐CD as binder. Combined with its low cost and environmental benignity, C‐ β ‐CD is a promising binder for sulfur cathodes in rechargeable lithium batteries with high electrochemical performance. The sulfur utilization and cycling stability of composite cathodes in rechargeable lithium batteries are enhanced by carbonyl‐ β ‐cyclodextrin (C‐ β ‐CD) as the binder in sulfur composite cathodes. This is made possible by the fact that C‐ β ‐CD is highly soluble in water, ca. 100 times more soluble than β ‐CD at room temperature, and because it exhibits strong bonding strength.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96706/1/adfm_201201847_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96706/2/1194_ftp.pd

Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapyopen

Anti-CV2/CRMP5 Paraneoplastic Chorea Effectively Managed with Intravenous Amantadine

Background: Paraneoplastic chorea is typically a subacute progressive hyperkinetic movement disorder. The mainstay of treatment is managing the underlying neoplasm. However, the clinical course may be variable, and effective symptomatic management can precede the start of cancer treatment. Case report: A 63-year-old man presented with insidious onset, slowly progressive generalized chorea for 1 year, later diagnosed as anti-CV2/CRMP5 autoantibody positive paraneoplastic chorea. His chorea was markedly improved with intravenous amantadine. Discussion: In patients with anti-CV2/CRMP5 autoantibody-related chorea, sequential follow-up of brain magnetic resonance imaging reveals progression from active inflammation to atrophy. Our report highlights the efficacy of intravenous amantadine in paraneoplastic chorea

Impact of mutations in DNA methylation modification genes on genome-wide methylation landscapes and downstream gene activations in pan-cancer

In cancer, mutations of DNA methylation modification genes have crucial roles for epigenetic modifications genome-wide, which lead to the activation or suppression of important genes including tumor suppressor genes. Mutations on the epigenetic modifiers could affect the enzyme activity, which would result in the difference in genome-wide methylation profiles and, activation of downstream genes. Therefore, we investigated the effect of mutations on DNA methylation modification genes such as DNMT1, DNMT3A, MBD1, MBD4, TET1, TET2 and TET3 through a pan-cancer analysis. First, we investigated the effect of mutations in DNA methylation modification genes on genome-wide methylation profiles. We collected 3,644 samples that have both of mRNA and methylation data from 12 major cancer types in The Cancer Genome Atlas (TCGA). The samples were divided into two groups according to the mutational signature. Differentially methylated regions (DMR) that overlapped with the promoter region were selected using minfi and differentially expressed genes (DEG) were identified using EBSeq. By integrating the DMR and DEG results, we constructed a comprehensive DNA methylome profiles on a pan-cancer scale. Second, we investigated the effect of DNA methylations in the promoter regions on downstream genes by comparing the two groups of samples in 11 cancer types. To investigate the effects of promoter methylation on downstream gene activations, we performed clustering analysis of DEGs. Among the DEGs, we selected highly correlated gene set that had differentially methylated promoter regions using graph based sub-network clustering methods. We chose an up-regulated DEGs cluster where had hypomethylated promoter in acute myeloid leukemia (LAML) and another down-regulated DEGs cluster where had hypermethylated promoter in colon adenocarcinoma (COAD). To rule out effects of gene regulation by transcription factor (TF), if differentially expressed TFs bound to the promoter of DEGs, that DEGs did not included to the gene set that effected by DNA methylation modifiers. Consequently, we identified 54 hypomethylated promoter DMR up-regulated DEGs in LAML and 45 hypermethylated promoter DMR down-regulated DEGs in COAD. Our study on DNA methylation modification genes in mutated vs. non-mutated groups could provide useful insight into the epigenetic regulation of DEGs in cancer.This research is supported by National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT (No. NRF-2017M3C4A7065887), the Collaborative Genome Program for Fostering New Post-Genome Industry of the National Research Foundation (NRF) funded by the Ministry of Science and ICT (MSIT) (No. NRF-2014M3C9A3063541), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3224). The funding bodies provided financial support but had no other role in the design of the study, data collection, analysis, and interpretation of data, decision to publish, or preparation of the manuscript

Effect of donor–recipient size mismatch on long-term graft survival in pediatric kidney transplantation: a multicenter cohort study

Background Donor–recipient size mismatching is commonly occurs in pediatric kidney transplantation (KT). However, its effect on graft survival remains unknown. This study aimed to determine the effect of donor–recipient size mismatch on the long-term survival rate of transplant kidneys in pediatric KT. Methods A total of 241 pediatric patients who received KT were enrolled. The medical records of all patients were retrospectively reviewed, and the correlation between donor–recipient size mismatch and graft function and long-term graft outcome was analyzed according to donor–recipient size mismatch. Results Recipients and donors’ mean body weight at the time of KT were 34.31 ± 16.85 and 56.53 ± 16.73 kg, respectively. The mean follow-up duration was 96.49 ± 52.98 months. A significant positive correlation was observed between donor–recipient body weight ratio (DRBWR) or donor–recipient body surface area ratio (DRBSR) and graft function until 1 year after KT. However, this correlation could not be confirmed at the last follow-up. The results of long-term survival analysis using Fine and Gray’s subdistribution hazard model showed no significant difference of the survival rate of the transplant kidney according to DRBWR or DRBSR. Conclusion Donor–recipient size mismatch in pediatric KT is not an important factor in determining the long-term prognosis of transplant kidneys

Power conversion efficiency enhancement based on the bio-inspired hierarchical antireflection layer in dye sensitized solar cells

We have investigated the effects of the introduction of an antireflection layer consisting of a hierarchically patterned diffraction grating into a conventional TiO2 working electrode on the power conversion efficiency (PCE) of a DSSC. High index-contrast TiO2 nanowires (NWs) were grown in the circular holes of the two-dimensional diffraction grating prepared through the use of a polymer template fabricated via interference lithography (IL) for maximized photon trapping effects in the visible region of light. The larger scale dimension of the polymer template was determined using the beam parameters of the IL and the smaller scale dimension in the structures was controlled by the growth conditions of the TiO2 NWs. Compared with a conventional DSSC, the hybrid nanostructure with an additional antireflection layer demonstrated higher and wider absorption bands of wavelength spectra, leading to an increased PCE due to enhanced light trapping effects achieved by the combination of antireflection and diffraction of the light on the front surface of the devices with minimum loss in the surface area of the hierarchical structure. The excellent performance of the optimized hybrid nanostructure indicates that the nanophotonic effects have strong potential for solar energy conversion, photocatalyst, and photoelectrode applications.close10

Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment

Peripheral blood stem cell (PBSC) mobilization, which uses plerixafor (AMD 3100), a newly developed specific inhibitor of the CXCR4 receptor, in combination with granulocyte-colony stimulating factor(G-CSF), has been shown to enhance the stem cell mobilization in adult patients, but pediatric data are scarce. We documented our experience with this drug in 6 Korean pediatric patients who had failed in chemomobilization, using G-CSF, alone. All patients were mobilized CD34+ cells (median, 11.08 × 106/kg: range, 6.34-28.97 × 106/kg) successfully within 2 to 3 cycles of apheresis, without complications. A total of 7 autologous transplantations were performed, including 1 tandem transplantation. However, 2 patients with brain tumors showed severe pulmonary complications, including spontaneous pneumomediastinum. This is the first study of PBSC mobilization with plerixafor in Asian pediatric patients. Furthermore our study suggests that mobilization with plerixafor may be effective in Korean pediatric patients, who have previously been heavily treated and have failed PBSC mobilization with classical chemomobilization, using G-CSF. However, further studies are needed to examine the possible complications of autologous transplantation, using a mobilized plerixafor product in children