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siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin

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World Journal of Gastroenterology 2012年第31期18卷 4127-4135页

作者： Md.Raghibul Hasan Shyam Singh Chauhan Rinu Sharma Ranju Ralhan Department of Biochemistry All India Institute of Medical SciencesNew Delhi 110029India Department of Biotechnology School of BiotechnologyGuru Gobind Singh Indraprastha UniversityNew Delhi 110075India Department of Otolaryngology-Head and Neck Surgery Joseph and Mildred Sonshine Family Centre for Head and Neck DiseasesMount Sinai HospitalTorontoON M5G 1X5Canada Department of Pathology and Laboratory Medicine Alex Simona Shnaider Laboratory for Molecular OncologyMount Sinai HospitalTorontoON M5G 1X5Canada

AIM： To determine the functional significance of TC21 in esophageal squamous cell carcinoma （ESCC）. METHODS： TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and tran- scripts were analyzed by reverse transcription-poly- merase chain reaction and protein by Western *** demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assess- ing the phosphorylation status of its downstream tar- gets, phosphoinositide 3-kinase （PI3K）, phosphatase and tensin homolog （PTEN）, protein kinase B （pAl〈t）, nuclear factor-KB （NF-~B） and cyclinD1 using specific antibodies. Cell survival analysis after cisplatin treat- ment was carried out by cell viability assay and cell cycle analysis using flow cytometry. RESULTS： TC21 knockdown in human ESCC cell line TEl3 cells, showed only a marginal increase （14.2%） in cell death compared with control cells. The expres- sions of the signaling proteins PI3K and pAkt, transcrip- tion factor NF-KB, and cell cycle protein cyclin D1 were markedly decreased in response to TC21 downregula- tion, whereas the level of pPTEN, an antagonist of PI3K, was increased. In addition, we evaluated the potential of TC21 as a putative target for sensitizing ESCC cells to the chemotherapeutic agent cisplatin. Increased cell death （38.4%） was observed in cells treated with cis- platin after TC21 knockdown compared with cells which were treated with cisplatin alone （20% cell death）. CONCLUSION： Results suggest that TC21 mediates its effects via the PI3K-Akt pathway, NF-KB and cyclin D1, and enhances chemoresistance in esophageal cancer cells.

关键词： TC21 Esophageal squamous cell carci-noma siRNA Cisplatin Chemosensitivity

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction

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Asian Journal of Andrology 2008年第3期10卷 495-502页

作者： Hui Meng Tan Chong Min Chin Chong Beng Chua Edsal Gatchalian Apichat Kongkanand Clarence Lei Chang Moh Foo Cheong Ng Krisada Ratana-Olarn Dennis Serrano Akmal Taher Ismail Tambi Anupan Tantiwong Michael Wong Yuet Chen Wai-Chun Yip Subang Jaya medical centre Selengor 47500 Malaysia National University Hospital Singapore 119074 University Malaya medical centre Kuala Lumpur 59100 Malaysia Manila Doctors Hospital Ermita Metro Manila the Philippines Chulalongkorn University Hospital Bangkok 10330 Thailand Normah Hospital 93050 Kuching Malaysia Changi General Hospital Singapore 529889 Ramathibodi Hospital Bangkok 10400 Thailand University of lndonesia Jakarta 10430 Indonesia Damai Service Hospital Kuala Lumpur 51200 Malaysia Siriraj Hospital Mahidol University 10700 Bangkok Thailand mount elizabeth medical centre Singapore228510 Kwong Wah Hospital Kowloon Hong Kong China

Aim： To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 （PDE-5） inhibitor, in men of Asian ethnicity with erectile dysfunction （ED）. Methods： In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil （10 mg） or placebo （4：1 ratio） for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain （IIEF-EF）, and Sexual Encounter Profile （SEP） questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question （GAQ） on erection improvement. Results： Least-squares mean baseline IIEF-EF domain scores （vardenafil 14.6, placebo 13.4） were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo （22.4 vs. 14.3; P 〈 0.001）. Vardenafil was associated with significant improvements from baseline in least squares （LS） mean success rates for SEP-2 （vardenafil 82.2 vs. placebo 43.6; P 〈 0.001） and SEP-3 （vardenafil 66.1 vs. placebo 24.0; P 〈 0.001）. Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. Conclusion： Vardenafil （10 mg） is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.

关键词： Asian males erectile dysfunction impotence phosphodiesterase inhibitors sexual dysfunction vardenafil

Ophthalmic manifestations in seropositive dengue fever patients during epidemics caused by predominantly different dengue serotypes

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Advances in Ophthalmology Practice and Research 2022年第2期2卷 18-24页

作者： Ajeet M.Wagle Smita R.Hegde Srinivasan Sanjay Kah-Guan Au Eong International Eye Cataract Retina centre Mount Elizabeth Medical CentreSingapore International Eye Cataract Retina centre Farrer Park Medical CentreSingapore Khoo Teck Puat Hospital Singapore Alexandra Hospital Singapore Shree Shantinath medical Trust-Jain Hospital MumbaiIndia Narayana Nethralaya BangaloreIndia Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore

Purpose:Dengue fever(DF)epidemics in Singapore in 2005–2006 and 2007 were caused predominantly by dengue virus serotypes 1(DENV-1)and 2(DENV-2)*** investigated the prevalence of ophthalmic manifestations during these consecutive ***:Seropositive DF patients admitted to the hospital during two separate dengue epidemics were enrolled from June 2005 to December ***,ophthalmic,and laboratory data were *** primary outcome measures were differences in ophthalmic and laboratory features across the two *** associated with increased risk of developing various DF-related ophthalmic manifestations were the secondary outcome ***:Of the 115 patients enrolled,109(94.7%;33 in 2005–2006 and 76 in 2007)completed the eye screening *** of patients were Chinese(65,59.6%)and males(81,74.3%).The mean age was 40.8 years(range,18–87).Colour vision impairment(12 vs 14[36.4%vs 18.7%];P?0.04),cotton wool spots(10 vs 3[30.3%vs 3.9%];P<0.001),bleeding diathesis(7 vs 3[21.2%vs 3.9%];P?0.004)and abnormal liver function(mean alanine amino-transferase[150.2 U/L vs 68.28 U/L;P?0.001],mean aspartate amino-transferase[196.86 U/L vs 99.53 U/L;P?0.002],total protein[68.43 g/L vs 72.27 g/L;P?0.016],serum albumin[36.86 g/L vs 40.5 g/L;P?0.001])were noted more often in DF epidemics predominantly caused by DENV-1 compared to ***:A higher prevalence of colour vision impairment,cotton wool spots,bleeding diathesis,and abnormal liver function was found in DF epidemics predominantly caused by DENV-1 compared to DENV-2.

关键词： Dengue fever Ophthalmic manifestations Serotype Epidemic Singapore

The role of radiotherapy in metastatic bladder cancer

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 553-563页

作者： Jananie Perera Peter Hoskin mount Vernon Cancer centre Rickmansworth RoadNorthwoodMiddlesex HA62RNUK Division of Cancer Sciences University of ManchesterManchester M204GJUK

The management of metastatic bladder cancer is *** outcomes are achieved in those who are fit enough for systemic *** place of radiotherapy in these patients is mainly for symptom control,in particular ***,a small proportion,especially those with oligometastases,will benefit from more radical *** this review,we look at the evidence currently available for radiotherapy in this setting.

关键词： Bladder cancer radiotherapy oligo metastases haematuria bone metastases brain metastases

Stream-dwelling fungal decomposer communities along a gradient of eutrophication unraveled by 454 pyrosequencing

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Fungal Diversity 2015年第1期70卷 127-148页

作者： S.Duarte F.Bärlocher J.Trabulo F.Cássio C.Pascoal centre of Molecular and Environmental Biology(CBMA) Department of BiologyUniversity of MinhoCampus de Gualtar4710-057 BragaPortugal Department of Biology Mount Allison UniversitySackvilleNB E4L 1G7Canada

Microbial decomposers,especially a fungal group called aquatic hyphomycetes,play a critical role in processing plant litter in freshwaters by increasing its palatability to invertebrate ***,communities of aquatic hyphomycetes have been assessed through the identification of spores,which misses non-sporulating *** new technologies,454 pyrosequencing stands out as most promising for large-scale species ***,very few attempts have been made to validate its effectiveness for assessing the diversity of stream-dwelling fungal *** attempted to gain greater insight into the diversity of aquatic fungal communities in streams exposed to various degrees of eutrophication by using the 454 pyrosequencing technology.A total of 173,889 ITS2 pyrosequencing reads with hits for fungi were obtained from the 5 investigated *** majority of operational taxonomic units(OTUs)belonged to Ascomycota and the identification to the genus level was achieved for 169 *** the total,135,257 reads(ca.78%)showed close affinities to aquatic hyphomycete *** showed declining fungal diversity in the most eutrophic streams,which was congruent with a reduced diversity found through spore *** patterns revealed by connecting representative OTUs to ITS sequences from aquatic hyphomycetes were similar to those determined by traditional spore identification ***,454 pyrosequencing provided a more comprehensive view of fungal diversity;it captured almost twice as many taxa as spore *** study vali-dates the effectiveness of 454 pyrosequencing for surveying the diversity of stream-dwelling fungal decomposer *** application may accelerate the use of these communities for monitoring the integrity of freshwaters.

关键词： Freshwater ecosystems Plant litter decomposition Aquatic fungi ITS region

A survey on the adoption of blockchain in IoT:challenges and solutions

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Blockchain(Research and Applications) 2021年第2期2卷 1-49页

作者： Md Ashraf Uddin Andrew Stranieri Iqbal Gondal Venki Balasubramanian Internet Commerce Security Laboratory Federation University AustraliaMount HelenBallaratVIC3350Australia

Conventional Internet of Things(IoT)ecosystems involve data streaming from sensors,through Fog devices to a centralized Cloud *** that arise include privacy concerns due to third party management of Cloud servers,single points of failure,a bottleneck in data flows and difficulties in regularly updating firmware for millions of smart devices from a point of security and maintenance *** technologies avoid trusted third parties and safeguard against a single point of failure and other *** has inspired researchers to investigate blockchain’s adoption into IoT *** this paper,recent state-of-the-arts advances in blockchain for IoT,blockchain for Cloud IoT and blockchain for Fog IoT in the context of eHealth,smart cities,intelligent transport and other applications are ***,research gaps and potential solutions are also presented.

关键词： Blockchain technology Consensus mechanism Blockchain cryptographic primitives healthcare Patient monitoring Cloud of Things Internet of Things Fog of Things Software defined network Blockchain applications

Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-pacific hepatitis C virus genotype 1 non-responders/relapsers

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World Journal of Gastroenterology 2015年第28期21卷 8660-8669页

作者： Wattana Sukeepaisarnjaroen Tri Pham Tewesak Tanwandee Saroja Nazareth Sam Galhenage Lindsay Mollison Leanne Totten Alan Wigg Rosalie Altus Anton Colman Brenda Morales Sue Mason Tracey Jones Nadine Leembruggen Vince Fragomelli Cheryl Sendall Richard Guan Dede Sutedja Soek Siam Tan Yock Young Dan Yin Mei Lee Widjaja Luman Eng Kiong Teo Yin Min Than Teerha Piratvisuth Seng Gee Lim Srinagarind Hospital Cabramatta Practice Siriraj Hospital Bangkok Royal Perth Hospital Fremantle Hospital Flinders medical centre Royal Adelaide Hospital Austin Hospital Royal Prince Alfred Hospital John Hunter Hospital Nepean Hospital Cairns Base Hospital mount elizabeth medical centre Gleneagles Hospital Selayang Hospital National University Health System Yong Loo Lin School of Medicine National University of Singapore Changi General Hospital NKC Institute of Gastroenterology and Hepatology Prince of Songkla University

AIM:To examined the efficacy and safety of treatment with boceprevir,PEGylated-interferon and ribavirin(PR)in hepatitis C virus genotype 1(HCVGT1) PR treatmentfailures in ***:The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR *** physicians were invited to contribute data from their patients:baseline characteristics,ontreatment responses,sustained virological response at week 12(SVR12),and safety were collected and *** analysis was performed to determine predictors of ***:150 patients were enrolled from Australia,Malaysia,Singapore and Thailand(Asians = 86,Caucasians = 63).Overall SVR12 was 61%(Asians= 59.3%,Caucasians = 63.5%).SVR12 was higher in relapsers(78%) compared with non-responders(34%).On-treatment responses predicted SVR,with undetectable HCVRNA at week 4,8 and 12 leading to SVR12 s of 100%,87%,and 82%respectively,and detectable HCVRNA at week 4,8 and 12,leading to SVR12 s of 58%,22%and 6%*** patients were similar to Caucasian patients with regards to on-treatment *** with cirrhosis(n= 69) also behaved in the same manner with regards to on-treatment *** with the IL28 B CC genotype(80%) had higher SVRs than those with the CT/TT(56%) genotype(P = 0.010).Multivariate analysis showed that TW8 and TW12 responses were independent predictors of *** adverse events occurred in 18.6%:sepsis(2%),decompensation(2.7%) and blood transfusion(14%).Discontinuations occurred in 30.7%,with 18.6%fulfilling stopping ***:Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80%if they have good on-treatment responses;however,discontinuations occurred in 30%because of virological failure or adverse events.

关键词： Chronic hepatitis C Treatment failure Rapid virological response Lead-in Null response Partial response Relapse Cirrhosis Response guidedtherapy

Numerical simulation of tumor blood perfusion based on 3D angiogenic microvasculature,investigation of effects of vascular normalization by anti-angiogenic therapy on tumor microenvironment

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Numerical simulation of tumor blood perfusion based on 3D an...

Numerical simulation of blood flow and interstitial fluid pressure in solid tumor microcirculation based on tumor-induced angiogenesis

2008年全国生物流变学与生物力学学术会议

作者： Anwar R.Padhani Paul Strickland Scanner centre Mount Vernon HospitalNorthwoodMiddlesexUK

The purpose of the study is to investigate blood perfusion in solid tumors,as well as the effects of vascular normalization by anti-angiogenic therapy on tumor ***.1 describes the major structure of the *** is based o...

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Acta Mechanica Sinica 2007年第5期23卷 477-483页

作者： Gaiping Zhao Jie Wu Shixiong Xu M. W. Collins Quan Long Carola S. Konig Yuping Jiang Jian Wang A. R. Padhani Department of Mechanics and Engineering Science Fudan University Shanghai 200433 China Brunel Institute for Bioengineering School of Engineering and Design Brunel University Uxbridge Middlesex UK Department of Neurology Huashan Hospital Fudan University Shanghai 200040 China Paul Strickland Scanner centre Mount Vernon Hospital Rickmansworth Road Northwood Middlesex HA6 2RN UK

A coupled intravascular-transvascular-interstitial fluid flow model is developed to study the distributions of blood flow and interstitial fluid pressure in solid tumor microcirculation based on a tumor-induced microvascular network. This is generated from a 2D nine-point discrete mathematical model of tumor angiogenesis and contains two parent vessels. Blood flow through the microvascular network and interstitial fluid flow in tumor tissues are performed by the extended Poiseuille＇s law and Darcy＇s law, respectively, transvascular flow is described by Starling＇s law; effects of the vascular permeability and the interstitial hydraulic conductivity are also considered. The simulation results predict the heterogeneous blood supply, interstitial hypertension and low convection on the inside of the tumor, which are consistent with physiological observed facts. These results may provide beneficial information for anti-angiogenesis treatment of tumor and further clinical research.

关键词： Solid tumor pressure-Angiogenesis Blood flow - Interstitial Numerical simulation