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| 1 | Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation显示文摘The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation. | Joyce YS Chow Chun K Wong Phyllis FY Cheung Christopher WK Lam | 2010 | Cellular & Molecular Immunology2010，7，1： | 22 |
| 2 | Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis显示文摘Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses.However,the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes(FLS)in rheumatoid arthritis(RA)have not been elucidated.Therefore,we investigated the in vitro effects of monosodium urate crystals,alone or in combination with the inflammatory cytokines tumor-necrosis factor(TNF)-a or interleukin(IL)-1b,on the activation of human FLS from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals.Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6,the chemokine CXCL8 and the matrix metalloproteinase(MMP)-1 from both normal and RA-FLS(all P,0.05).Moreover,the additive or synergistic effect on the release of IL-6,CXCL8 and MMP-1 from both normal and RA-FLS was observed following the combined treatment with monosodium urate crystals and TNF-a or IL-1b.Further experiments showed that the release of the measured inflammatory cytokine,chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway.Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA. | Da P Chen Chun K Wong Lai S Tam Edmund K Li Christopher WK Lam | 2011 | Cellular & Molecular Immunology2011，8，6： | 5 |
| 3 | Ipsilateral breast tumor recurrence in early stage breast cancer patients treated with breast conserving surgery and adjuvant radiation therapy: Concordance of biomarkers and tumor location from primary tumor to in-breast tumor recurrence显示文摘BACKGROUND Patients with an in-breast tumor recurrence(IBTR)after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality.Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge.AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes.METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution.Overall survival(OS),disease-free survival,and local recurrence-free survival(LRFS)were estimated using the Kaplan Meier method.We identified patients who experienced an isolated IBTR.Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated.The effect of clinical and treatment parameters on disease outcomes was also evaluated.RESULTS We identified 2164 patients who met the eligibility criteria.The median follow-up for all patients was 3.73[interquartile range(IQR)2.27-6.07]years.Five-year OS was 97.7%(95%CI:96.8%-98.6%)with 28 deaths;5-year LRFS was 98.0%(97.2-98.8)with 31 IBTRs.We identified 37 patients with isolated IBTR,19(51.4%)as ductal carcinoma in situ and 18(48.6%)as invasive disease,of whom 83.3%had an in situ component.Median time from initial diagnosis to IBTR was 1.97(IQR:1.03-3.5)years.Radiotherapy information was available for 30 of 37 patients.Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed.Twenty-five of thirty-two(78.1%)patients had concordant hormone receptor status,HER-2 receptor status,and estrogen receptor(ER)(P=0.006)and progesterone receptor(PR)(P=0.001)status from primary to IBTR were significantly associated.There were no observed changes in HER-2 status from primary to IBTR.The concordance between quadrant of primary to IBTR was 10/19[(62.2%),P=0.008].Tumor size greater than 1.5 cm(HR=0.44,95%CI:0.22-0.90,P=0.02)and use of endocrine therapy upfront(HR=0.36,95%CI:0.18-0.73,P=0.004)decreased the risk of IBTR.CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT,ER/PR status and quadrant were highly concordant from primary to IBTR.Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR. | Juhi M Purswani Fauzia Shaikh S Peter Wu Jennifer Chun Kim Freya Schnabel Nelly Huppert Carmen A Perez Naamit K Gerber | 2020 | World Journal of Clinical Oncology2020，11，1： | 2 |
| 4 | Radical prostatectomy in patients aged 75 years or older:review of the literature显示文摘Given the demographic trends toward a considerably longer life expectancy,the percentage of elderly patients with prostate cancer will increase further in the upcoming decades.Therefore,the question arises,should patients ≥75 years old be offered radical prostatectomy and under which circumstances? For treatment decision-making,life expectancy is more important than biological age.As a result,a patient's health and mental status has to be determined and radical treatment should only be offered to those who are fit.As perioperative morbidity and mortality in these patients is increased relative to younger patients,patient selection according to comorbidities is a key issue that needs to be addressed.It is known from the literature that elderly men show notably worse tumor characteristics,leading to worse oncologic outcomes after treatment.Moreover,elderly patients also demonstrate worse postoperative recovery of continence and erectile function.As the absolute rates of both oncological and functional outcomes are still very reasonable in patients ≥75 years,a radical prostatectomy can be offered to highly selected and healthy elderly patients. Nevertheless,patients clearly need to be informed about the worse outcomes and higher perioperative risks compared to younger patients. | Philipp Mandel Thenappan Chandrasekar Felix K Chun Hartwig Huland Derya Tilki | 2019 | Asian Journal of Andrology2019，21，1： | 2 |
| 5 | Efficient Generation at 421 nm by resonantly enhanced doubling of GaAlAs laser diode array emission 显示文摘 | Coldkey L Chun M K | 1989 | Applied physics letter1989，55，3： | 1 |
| 6 | Epidermoid cyst of the testis:a report of three cases and an analysis of 141 cases from the world literature显示文摘 | Shah K H MaxtedWC Chun B | 1981 | Cancer1981，17，3： | 1 |
| 7 | Neurological injuryand recover in pations the burst fracture of the tho-racolumbar spine显示文摘 | Kim N H Lee H K Chun I M | 1999 | Spine1999，24，3： | 1 |
| 8 | Phase Equilibria of Methane and Carbon Dioxide Hydrates in the Aqueous MgC12 Solu- tions 显示文摘 | Kang S P Chun M K Lee H | 1998 | Fluid Phase Equilibria1998，147，12： | 1 |
| 9 | A novel startup scheme of stator-flux-oriented vector-controlled induction motor drive without torque jerk显示文摘 | Chun T W Choi M K Bose B K | 2003 | IEEE Transactions on Industry Applications2003，39，3： | 1 |
| 10 | MR-387 A and B, new aminopeptidase N inhibitors, produced by Streptomyces neyagawaensis SL-387显示文摘 | Chung M C Chun H K Han K H | 1996 | J Antibiot (Tokyo)1996，49，1： | 1 |
| 11 | The temperature effects on hydraulic conductivity of compacted bentonite显示文摘 | CHOW J LEE J O CHUN K S | 1999 | Applied Clay Science1999，14，1： | 1 |
| 12 | Simulation for the propulsion of a micro-hydro robot with an unstructured grid显示文摘 | KIM M C KANG H K CHUN H H | 2008 | Ocean Engineering2008，35，： | 1 |
| 13 | Fabrication of dye-sensitized solar cells u-sing Ti02-nanotube arrays on Ti-grid substrates显示文摘 | Chun K Y | 2009 | ThinSolid Films2009，517，： | 1 |
| 14 | Phylogenetic analysis of Bacillus subti- lis and related taxa based on partial gyrA gene sequences 显示文摘 | Chun J Bae K S | 2000 | Antonie van Leeuwenhoek2000，78，2： | 1 |
| 15 | Genetic analysis of patients with the Saethre-Chotzen phenotype 显示文摘 | Chun K Teebi AS Jung JH | 2002 | Am J Med Genet2002，110，2： | 1 |
| 16 | Performance of three-phase three-dimensional electrode reactor for the reduction of COD in simulated wastewater-containing phenol显示文摘 | Ya Xiong Chun He Hans T K | | 0，，01： | 1 |
| 17 | Application of factorial design to accelerate identification of CHO growth factor requirements显示文摘 | Chun C Heineken K Szeto D | | 0，，01： | 1 |
| 18 | Inhibitory effects of 6-gingerol,a major pungent principle of ginger,on phorbol ester induced inflammation, epidermal omithine decarboxylase activity and skin tumor promotion in ICR mice显示文摘 | PARK K K CHUN K S LEE J M | 1998 | Cancer letter1998，129，2： | 1 |
| 19 | Thrce-dimensional metalorganic framework with (3,4) -connected net, synthesized from an ionic liquid medium 显示文摘 | Dybtsev D N Chun H Kim K | 2004 | Chem Commun2004，14，： | 1 |
| 20 | Mechanisms for inhibition of hepatitis B virus gene expression and replication by hepatitis C virus core protein显示文摘 | Shiow Y C Chih F K Chun M C | 2003 | J Biol Chem2003，278，： | 1 |
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