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      • Treatment Outcomes for Radiotherapy Alone are Comparable With Neoadjuvant Chemotherapy Followed by Radiotherapy in Early-Stage Nasopharyngeal Carcinoma

        Song, Chang Hoon,Wu, Hong-Gyun,Heo, Dae Seog,Kim, Kwang Hyun,Sung, Myung-Whun,Park, Charn Il The American Laryngological, Rhinological Otologic 2008 The Laryngoscope Vol.118 No.4

        OBJECTIVES:: To analyze the impact of neoadjuvant chemotherapy (CT) on the treatment of early-stage nasopharyngeal carcinoma (NPC) as compared with radiotherapy (RT) alone. METHODS:: We analyzed retrospectively the outcome of 60 previously untreated and histologically confirmed early-stage NPC patients treated with either RT alone or with neoadjuvant CT followed by RT (CT/RT) at the Seoul National University Hospital between 1986 and 2004. Neoadjuvant CT consisted of three cycles with 5-fluourouracil and cisplatin. RT was given to the nasopharynx and neck nodes. The median dose to the primary site, involved nodes, and elective nodes was 70.2 Gy, 63 Gy, and 45 Gy, respectively. According to the 1997 American Joint Committee on Cancer staging system, 9 patients had stage I or IIA disease, and 22 patients had stage IIB disease in the RT group. For the CT/RT group, 8 patients had stage I or IIA disease, and 21 patients had stage IIB disease. The median follow-up for all patients was 124.5 (range, 5–239) months. RESULTS:: The 5-year locoregional failure-free (LRFF), distant metastasis-free (DMF), disease-free survival (DFS), and overall survival (OS) rate was 84%, 93%, 81%, and 84% for the RT group and 77%, 86%, 71%, and 79% for the CT/RT group, respectively. There were no significant differences in LRFF (P = .728), DMF (P = .433), DFS (P = .562), and OS (P = .625) rates between the RT and CT/RT groups. Multivariate analysis revealed that delaying RT for more than 81 days was significantly associated with an increased risk of locoregional failure in the subgroup of patients with stage IIB disease (P = .044). CONCLUSIONS:: In our retrospective analysis, the use of neoadjuvant CT showed no additional benefit to treatment with RT alone. Neoadjuvant CT may cause deleterious effect on stage IIB disease by delaying RT.

      • Therapeutic effect of recombinant human epidermal growth factor (rhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer : A double-blind placebo-controlled prospective phase 2 multi-institutional c

        Wu, Hong Gyun,Song, Si Yeol,Kim, Yeon Sil,Oh, Young Taek,Lee, Chang Geol,Keum, Ki Chang,Ahn, Yong Chan,Lee, Sang-wook Wiley Subscription Services, Inc., A Wiley Company 2009 Cancer Vol.115 No.16

        <B>BACKGROUND:</B><P>We evaluated the efficacy of topically applied human recombinant epidermal growth factor (rhEGF) for the treatment of oral mucositis induced by radiotherapy (RT), with or without chemotherapy, in patients with head and neck cancer.</P><B>METHODS:</B><P>Patients receiving definitive chemoradiotherapy, definitive RT, or postoperative RT to the oral cavity or oropharynx were recruited from 6 institutions and enrolled in a randomized, double-blind, placebo-controlled phase 2 trial. Patients were assigned to a placebo group or to 1 of 3 EGF-treatment groups (10, 50, or 100 μg/mL doses, delivered in a spray, twice daily). The grade of mucositis was evaluated using the Radiation Therapy Oncology Group (RTOG) scoring criteria. Responders to EGF were defined as having an RTOG grade of 2 or lower at the fourth- or fifth-week examinations during RT, but an enduring RTOG grade 2 for 2 weeks was an exception.</P><B>RESULTS:</B><P>Of the 113 patients included in the study, 28 received placebo and 29 received EGF at 10 μg/mL, 29 at 50 μg/mL, and 27 at 100 μg/mL. EGF significantly reduced the incidence of severe oral mucositis at the primary endpoint (a 64% response was observed with 50 μg/mL EGF vs a 37% response in the control group; P = .0246).</P><B>CONCLUSIONS:</B><P>The EGF oral spray may have potential benefit for oral mucositis in patients undergoing RT for head and neck cancer. Phase 3 studies are ongoing to confirm these results. Cancer 2009. © 2009 American Cancer Society.</P>

      • KCI등재

        Can CD44+/CD24- Tumor Cells Be Used to Determine the Extent of Breast Cancer Invasion Following Neoadjuvant Chemotherapy?

        Hong Wu,Ruhui Li,XiaoDong Hang,Ming Yan,Feng Niu,Lidi Liu,Wei Liu,Song Zhao,Shaokun Zhang 한국유방암학회 2011 Journal of breast cancer Vol.14 No.3

        Purpose: To investigate the distribution of CD44+/CD24- cells in breast cancers in relation to tumor size before and after the administration of neoadjuvant chemotherapy. Methods: CD44+/CD24- tumor cells obtained from breast cancer specimens were characterized in vivo and in vitro using tumor formation assays and mammosphere generation assays, respectively. The distribution of CD44+/CD24- tumor cells in 78 breast cancer specimens following administration of neoadjuvant chemotherapy was also evaluated using immunofluorescence assays, and this distribution was compared with the extent of tumor invasion predicted by Response Evaluation Criteria in Solid Tumours (RECIST). Results: In 27/78 cases, complete remission (CR) was identified using RECIST. However, 18 of these CR cases were associated with a scattered distribution of tumor stem cells in the outline of the original tumor prior to neoadjuvant chemotherapy. After neoadjuvant chemotherapy, 24 cases involved cancer cells that were confined to the tumor outline, and 21 cases had tumor cells or tumor stem cells overlapping the tumor outline. In addition, there were 6 patients who were insensitive to chemotherapy, and in these cases, both cancer cells and stem cells were detected outside the contours of the tumor volume imaged prior to chemotherapy. Conclusion:CD44+/CD24- tumor cells may be an additional parameter to evaluate when determining the extent of breast cancer invasion.

      • SCISCIESCOPUS

        External electric field induced hydrogen storage/release on calcium-decorated single-layer and bilayer silicene

        Song, Er Hong,Yoo, Sung Ho,Kim, Jae Joon,Lai, Shiau Wu,Jiang, Qing,Cho, Sung Oh The Royal Society of Chemistry 2014 Physical chemistry chemical physics Vol.16 No.43

        <P>Hydrogen storage and release are two essential parameters that define the efficiency of a hydrogen storage medium. Herein, we investigate the effects of the external electric field <I>F</I> on the adsorption–desorption of H<SUB>2</SUB> on a Ca-decorated silicene system (Ca–silicene) based on density functional theory calculations. Our study demonstrates that nine H<SUB>2</SUB> molecules per Ca atom can be adsorbed and 6.4 wt% H<SUB>2</SUB> can be adsorbed on Ca–silicene with an average binding energy of 0.19 eV per H<SUB>2</SUB>, while the appropriate <I>F</I> can be used to effectively enhance the hydrogen storage–release on the Ca–silicene system. The high synergetic effect may be attributed to the observation that <I>F</I> induces an enhancement of the charge transfer between H<SUB>2</SUB> molecules and the Ca–silicene system. Thus, the Ca–silicene system together with the synergy of <I>F</I> can efficiently facilitate H<SUB>2</SUB> adsorption–desorption, completing the whole hydrogen storage–release cycle.</P> <P>Graphic Abstract</P><P>The appropriate <I>F</I> can be used to effectively enhance the hydrogen storage–release on the Ca–silicene system. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c4cp02638a'> </P>

      • Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

        Song, C.,Hong, B.J.,Bok, S.,Lee, C.J.,Kim, Y.E.,Jeon, S.R.,Wu, H.G.,Lee, Y.S.,Cheon, G.J.,Paeng, J.C.,Carlson, D.J.,Kim, H.J.,Ahn, G.O. Pergamon Press 2016 International journal of radiation oncology, biolo Vol.95 No.3

        <P>Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [F-18]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day -1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 +/- 0.483 at day -1, 1.67 +/- 0.116 at day 0, 2.92 +/- 0.334 at day 2, and 2.13 +/- 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 coimmunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased slightly by day 6. Our results indicate that single high-dose irradiation can produce a rapid, but reversible, vascular collapse in tumors. (C) 2016 Elsevier Inc. All rights reserved.</P>

      • KCI등재

        Association analysis of polymorphisms of G protein-coupled receptor 54 gene exons with reproductive traits in Jiaxing Black sows

        Fen Wu,Wei Zhang,Qian-Qian Song,Hai-Hong Li,Ming-Shu Xu,Guoliang Liu,Jin-Zhi Zhang 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.8

        Objective: The aim of this study was to detect single nucleotide polymorphisms (SNP) of G protein-coupled receptor 54 (GPR54) gene and explore association of this candidate gene with reproductive traits in Jiaxing Black sows. Methods: Six pairs of primers of the gene were designed to amplify all exons thus sequences of which were detected by means of direct sequencing and then SNP loci were scanned. The effects of SNPs on total number of piglets born (TNB), number of piglets born alive (NBA), number of still born piglets (NSB), and litter weight at birth (LWB) of Jiaxing Black sows were analyzed. Results: Three SNP loci, including T3739C, C3878T and T6789C, were identified via comparison of sequencing and two genotypes (AB, BB) at each SNP site were observed. T3739C resulted in the change of amino acid (Leu→Pro) in corresponding protein, and C3878T resulted in synonymous mutation (Ile→Ile). Statistical results demonstrated that allele B was the preponderant allele at the three SNP loci and Genotype BB was the preponderant genotype. Meanwhile, Chi-Square test of these three SNPs indicated that all mutation sites fitted in Hardy-Weinberg equilibrium (p>0.05). For GPR54-T3739C locus, Jiaxing Black sows with genotype BB had 1.23 TNB and 1.28 NBA (p<0.01) that were more than those with genotype AB, respectively. Jiaxing Black sows that had the first two parities with genotype BB had additional 2.23 TNB, 2.27 NBA (p<0.01), and 1.94 LWB (p<0.05) compared to those with genotype AB, respectively. However, for other two loci, no significant difference was found between TNB, NBA, NSB, and LWB, and different genotypes of Jiaxing Black sows. Conclusion: In conclusion, the polymorphisms of GPR54-T3739C locus were significantly associated to TNB, NBA, and LWB and could be used as a potential genetic marker to improve reproductive function of Jiaxing black sows.

      • KCI등재

        Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells

        Peng Song,Yang Hai,Xin Wang,Longhe Zhao,Baoqiang Chen,Peng Cui,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.4

        Realgar (As4S4), as an arsenic sulfide mineraldrug, has a good therapeutic reputation for anticancer inTraditional Chinese Medicine, and has recently beenreported to inhibit angiogenesis in tumor growth. However,considering the poor solubility and low bioavailability ofrealgar, large dose of realgar and long period of treatmentare necessary for achieving the effective blood medicineconcentration. In present study, we resolved the crucialproblem of poor solubility of realgar by using intrinsicbiotransformation in microorganism, and investigatedunderlying mechanisms of realgar transforming solution(RTS) for antiangiogenesis. Our results demonstrated thatRTS had a strong activity to inhibit HUVECs proliferation,migration, invasion, and tube formation. Moreover, RTSinhibited VEGF/bFGF-induced phosphorylation ofVEGFR2 and the downstream protein kinases includingERK, FAK, and Src. In vivo zebrafish and chickenchorioallantoic membrane model experiments showed thatRTS remarkably blocked angiogenesis. Finally, comparedwith the control, administration of 2.50 mg/kg RTSreached more than 50% inhibition against H22 tumorallografts in KM mice, but caused few toxic effects in thehost. The antiangiogenic effect was indicated by CD31immunohistochemical staining and alginate-encapsulatedtumor cell assay. In summary, our findings suggest thatRTS inhibits angiogenesis and may be a potential drugcandidate in anticancer therapy.

      • A Novel Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivative, N25, Exhibiting Improved Antitumor Activity in both Human U251 and H460 Cells

        Zhang, Song,Huang, Wei-Bin,Wu, Li,Wang, Lai-You,Ye, Lian-Bao,Feng, Bing-Hong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

        $N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

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