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

Akt1-Inhibitor of DNA binding2 is essential for growth cone formation and axon growth and promotes central nervous system axon regeneration.

Mechanistic studies of axon growth during development are beneficial to the search for neuron-intrinsic regulators of axon regeneration. Here, we discovered that, in the developing neuron from rat, Akt signaling regulates axon growth and growth cone formation through phosphorylation of serine 14 (S14) on Inhibitor of DNA binding 2 (Id2). This enhances Id2 protein stability by means of escape from proteasomal degradation, and steers its localization to the growth cone, where Id2 interacts with radixin that is critical for growth cone formation. Knockdown of Id2, or abrogation of Id2 phosphorylation at S14, greatly impairs axon growth and the architecture of growth cone. Intriguingly, reinstatement of Akt/Id2 signaling after injury in mouse hippocampal slices redeemed growth promoting ability, leading to obvious axon regeneration. Our results suggest that Akt/Id2 signaling is a key module for growth cone formation and axon growth, and its augmentation plays a potential role in CNS axonal regeneration

Penetration Pathways Induced by Low-Frequency Sonophoresis with Physical and Chemical Enhancers: Iron Oxide Nanoparticles versus Lanthanum Nitrates

Low-frequency sonophoresis (LFS) has been shown to disrupt the structure of stratum corneum (SC) lipid bilayers and enhance SC permeability. In this study, we examined the penetration pathway of lanthanum nitrate (LaNO3) tracer in viable epidermis after combined treatment of LFS and tape stripping (TS), as a physical enhancer, or oleic acid (OA) application, as a chemical enhancer, using transmission electron microscopy (TEM). As a positive control, we visualized the passive diffusion pathway of LaNO3 and iron oxide (Fe3O4) nanoparticles after the incision of hairless mouse skin. Next, we applied LFS immediately after TS or OA application and visualized the penetration pathway of LaNO3. Each treatment showed restricted penetration to the SC–stratum granulosum (SG) interface or upper SG layer. However, the additional application of LFS induced diffuse intracellular distribution of LaNO3 throughout the viable epidermis. Quantitative analysis also revealed that combined treatment significantly increases LaNO3 penetration into viable epidermis when compared with each treatment. Our ultrastructural findings show the synergistic effect of LFS and TS or OA application on transdermal drug delivery. We also found that this combined treatment enhances the penetration of LaNO3 through the viable epidermis through an intracellular pathway

Dual Effect of Chrysanthemum indicum

The risk of bone-related diseases increases due to the imbalance between bone resorption and bone formation by osteoclasts and osteoblasts, respectively. The goal in the development of antiosteoporotic treatments is an agent that will improve bone through simultaneous osteoblast stimulation and osteoclast inhibition without undesirable side effects. To achieve this goal, numerous studies have been performed to identify novel approaches using natural oriental herbs to treat bone metabolic diseases. In the present study, we investigated the effect of Chrysanthemum indicum extract (CIE) on the differentiation of osteoclastic and osteoblastic cells. CIE inhibited the formation of TRAP-positive mature osteoclasts and of filamentous-actin rings and disrupted the bone-resorbing activity of mature osteoclasts in a dose-dependent manner. CIE strongly inhibited Akt, GSK3β, and IκB phosphorylation in RANKL-stimulated bone marrow macrophages and did not show any effects on MAP kinases, including p38, ERK, and JNK. Interestingly, CIE also enhanced primary osteoblast differentiation via upregulation of the expression of alkaline phosphatase and the level of extracellular calcium concentrations during the early and terminal stages of differentiation, respectively. Our results revealed that CIE could have a potential therapeutic role in bone-related disorders through its dual effects on osteoclast and osteoblast differentiation

Fifteen Years After the Gozan-Dong Glass Fiber Outbreak, Incheon in 1995

Objectives: In 1995, an outbreak survey in Gozan-dong concluded that an association between fiberglass exposure in drinking water and cancer outbreak cannot be established. This study follows the subjects from a study in 1995 using a data linkage method to examine whether an association existed. The authors will address the potential benefits and methodological issues following outbreak surveys using data linkage, particularly when informed consent is absent. Methods: This is a follow-up study of 697 (30 exposed) individuals out of the original 888 (31 exposed) participants (78.5%) from 1995 to 2007 assessing the cancer outcomes and deaths of these individuals. The National Cancer Registry (KNCR) and death certificate data were linked using the ID numbers of the participants. The standardized incidence ratio (SIR) and standardized mortality ratio (SMR) from cancers were calculated by the KNCR. Results: The SIR values for all cancer or gastrointestinal cancer (GI) occurrences were the lowest in the exposed group (SIR, 0.73; 95% CI, 0.10 to 5.21; 0.00 for GI), while the two control groups (control 1: external, control 2: internal) showed slight increases in their SIR values (SIR, 1.18 and 1.27 for all cancers; 1.62 and 1.46 for GI). All lacked statistical significance. All-cause mortality levels for the three groups showed the same pattern (SMR 0.37, 1.29, and 1.11). Conclusions: This study did not refute a finding of non-association with a 13-year follow-up. Considering that many outbreak surveys are associated with a small sample size and a cross-sectional design, follow-up studies that utilize data linkage should become standard procedure.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/0000040632/15SEQ:15PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:0000040632ADJUST_YN:YEMP_ID:A077602DEPT_CD:902CITE_RATE:0FILENAME:fifteen years after the gozan-dong glass fiber outbreak, incheon in 1995..pdfDEPT_NM:보건학과CONFIRM:

Comparative analysis of gut microbiota in elderly people of urbanized towns and longevity villages

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background To understand differences in the gut microbiota between elderly people of urbanized town communities (UTC) and longevity village communities (LVC), we analyzed fecal microbiota collected from individuals living in 2 UTC (Seoul and Chuncheon) and 3 LVC (Gurye, Damyang, and Soonchang) selected on the basis of indices for superlongevity (the ratio of centenarians to the total population) and longevity (the ratio of those aged 85 years or greater to those aged 65 years or greater) in South Korea by 454 pyrosequencing. Results Taxonomy-based analysis showed that The relative abundance of Firmicutes, Tenericutes, and Actinobacteria was significantly lower in LVC than in UTC. Due to an increase of Firmicutes and a reduction of Bacteroidetes, the ratio of Firmicutes to Bacteroidetes in the gut microbiota was greater in UTC adults than in UTC children or LVC adults. The population levels of Bacteroides, Prevotella, and Lachnospira were significantly higher in LVC than in UTC, but the levels of Dialister, Subdoligranulum, Megamonas, EF401882_g, and AM275436_g were lower in LVC than in UTC. Although most of the species detected in LVC were detected in UTC, some Bacteroides spp. and Faecalibacterium spp. were detected only in LVC. Among Bacteroides spp., ACWH_s, EF403317_s, and EF403722_s were detected in children and LVC samples only but FJ363527_s, 4P000677_s, and 4P000015_s were detected in UTC samples. EF402172_s and EF404388_s, members of Faecalibacterium spp., which are known to have anti-inflammatory properties, were detected in LVC and children only (>3.9% of total sequence). In addition, the fecal lipopolysaccharides (LPS) content was significantly higher in UTC than in LVC. Conclusions These findings suggest that maintaining gut microbiota, including Faecalibacterium spp. EF402172_s and EF404388_s, as well as low LPS levels may play an important role in preserving residents health in LVC