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Geldanamycin Combination with Colcemid Induces Mitotic Arrest through Stabilization of bubR1 Mitotic Kinase in Human Tumor Cells

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Journal of Cancer Therapy 2013年第3期4卷 709-719页

作者： Pitke vikrant Vinay Lebaka Prasanna Anjaneya Reddy Jonnala Ujwal Kumar Sugunan Sreedevi Upasana Sarangi Amere Subbarao Sreedhar CSIR—Centre for Cellular and Molecular Biology Hyderabad India

Mitosis-targeted anti-cancer therapies gained much attention in recent years. However, lack of tumor selectivity poses limitations to the current anti-mitotic drugs to be used as broad-spectrum anti-cancer agents. In this study, we show that combination treatment of colcemid, an inhibitor of microtubule polymerization with geldanamycin, an inhibitor of cancer chaperone, Hsp90 irreversibly targets mitosis through mitotic kinase bubR1 stabilization. When the individual and combination drugs treatments were tested against tumor cells (IMR-32 and HeLa) and non-tumor cells (SRA01), the combination treatment showed significant increase in cytotoxicity only in tumor cells followed by G2/M cell cycle block. The IMR-32 cells showed enhanced cytotoxicity in response to combination treatments, compared to HeLa cells. Further studies revealed that the G2/M arrest in IMR-32 correlates with both increased bubR1 nuclear localization and metaphase arrest. The siRNA knockdown of bubR1 has decreased tumor cell response to geldanamycin suggesting Hsp90-dependent regulation of bubR1. The combination treatment also showed inactivation of non-canonical β-catenin signaling suggesting inhibition of cancer growth. In addition, the combination treatment has significantly affected the distribution and functions of bubR1 downstream mitotic kinases such as aurks and plk1 indicating the combinatorial attack of combination treatment. In conclusion, we demonstrate that colcemid and GA combination treatment compromises the division potential of tumor cells interfering with the mitosis through bubR1 kinase.

关键词： Hsp90 Geldanamycin bubR1 Cell Cycle Tumor Cells

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Allgrove综合征临床特征及遗传学研究进展

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兰州大学学报（医学版） 2020年第3期46卷 1-6,14页

作者：姜倩 vikrant S.Tumbahangphe 陈慧兰州大学第二医院内分泌与代谢科甘肃兰州730030

Allgrove综合征是一种罕见的常染色体隐性遗传疾病,以无泪症、贲门失弛缓、原发性肾上腺皮质功能减退、神经系统功能障碍四联症为特征性表现。其致病基因为AAAS基因,该基因编码的ALADIN蛋白分布于肾上腺、胃肠道及大脑等全身各器官组织... 详细信息

Allgrove综合征是一种罕见的常染色体隐性遗传疾病,以无泪症、贲门失弛缓、原发性肾上腺皮质功能减退、神经系统功能障碍四联症为特征性表现。其致病基因为AAAS基因,该基因编码的ALADIN蛋白分布于肾上腺、胃肠道及大脑等全身各器官组织。AAAS基因突变导致ALADIN蛋白功能障碍为其根本原因。Allgrove综合征患者临床特征不尽相同,基因突变类型各异,并且无特定的基因型-表型相关性。本研究综述Allgrove综合征的临床表现及遗传学研究,助临床医生尽早识别该疾病并给予恰当干预。

关键词： Allgrove综合征 AAAS基因 ALADIN蛋白

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Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

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World Journal of Hepatology 2014年第5期6卷 358-362页

作者： vikrant Sood Rajeev Khanna Seema Alam Dinesh Rawat Shorav Bhatnagar Archana Rastogi Departments of Pediatric Hepatology Radiology and Pathology Institute of Liver and Biliary Sciences New Delhi 110070 India

An eleven-year-old clinically dysmorphic and devel-opmentally retarded male child presenting with com-plaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic porto-caval shunt(Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were con-firmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed.

关键词： Congenital extrahepatic portocaval shunt Ductal paucity Warkany syndrome Trisomy 8

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A Ginzburg—Landau Model for Linear Global Modes in Open Shear Flows

A Ginzburg—Landau Model for Linear Global Modes in Open She...

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第十一届全国流体力学学术会议

作者： Gupta vikrant He Wei Li Larry K.B 陈十一万敏平广东省湍流研究与应用重点实验室南方科技大学南方科技大学机械与航空航天工程系 School of Engineering University of Liverpool Department of Mechanical and Aerospace Engineering The Hong Kong University of Science & Technology 北京大学工程学院湍流与复杂系统国家重点实验室

The Ginzburg—Landau equation(GLE) can phenomenologically model several important features of non-equilibrium systems including those in fluid *** we show that the linear GLE can be formulated such that it has the same Wentzel—Kramers—Brillouin(WKB) approximation as for the linear global stability problem in open shear *** use the GLE to model the linear global modes of different wakes and find that it can accurately capture the linear growth rate and frequency to first order in the WKB ***,we find that it can also provide the shapes of the direct and adjoint eigenvectors and the regions of maximal structural *** proposed model thus opens up new possibilities for GLE-based control strategies,as well as it makes accurate stability calculations possible even for some computationally intractable open shear flows.

关键词： Flow instability Ginzburg—Landau model WKB approximation Wakes

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Scaling for Plate Specimens Subjected to Buried Blast Loading

Scaling for Plate Specimens Subjected to Buried Blast Loadin...

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第十三届全国实验力学学术会议

作者： Michael A.Sutton Xing Zhao Stephen R.McNeill vikrant Tiwari Xiaomin Deng William L.Fourney Uli Leiste Dept of Mechanical Engineering University of South CarolinaColumbiaSC 29208 Department of Aerospace Engineering University of MarylandMD 20742

Dimensional analysis is performed to develop appropriate parameters to guide the design of a set of scaled experimental *** assess the quality of the scaling predictions for the response of the scaled structures,high-speed stereo-vision system is *** are reported for surface deformations during the blast loading process,including 3D surface displacements,surface strain components and surface velocity and acceleration *** indicates that scaling for both(a) temporal variations and(b) spatial variations results in good agreement throughout the measurement period,demonstrating conclusively that scaling of small specimen measurements can be applied to quantitatively predict the dynamic response of larger plates.

关键词： Blast loading dynamic deformation high speed VIC-3D

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印度传统药物在癌症治疗中的应用(英文)

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中西医结合学报 2009年第11期7卷 1096-1099页

作者： Sunyana JAIN vikrant GILL Neeru VASUDEVA Neelam SINGLA Department of Pharmacy Advance Institute of Technology Ranbaxy Laboratories Ltd Clinical Pharmacology and Pharmacokinetic Department Department of Pharmaceutical Sciences Guru Jambheshwar University of Science and Technology

Cancer is one of the dreadful diseases of 20thcentury and moving vastly towards 2lst *** to the studies,world wide about 6 mil-lion new incidences are relgorted every year~[1].Itis the second maior cause of death aft... 详细信息

关键词：医学印度传统肿瘤植物药疗法

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Efficacy and Safety of Tinefcon^® Tablets in Subjects with Plaque Psoriasis: An Open Label, Non-Comparative, Multicenter, Phase IV Trial

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Journal of Cosmetics, Dermatological Sciences and Applications 2016年第2期6卷 55-66页

作者： Somesh Sharma Kailash Bhatia Meetesh Agarwal Sandesh Gupta Leelavathi Budamakuntla Sudhakar Grandhi Vinod Titarmare Sushil Pande Ranjan Rawal Aruna Samarth Rizwan Haq vikrant Saoji D. V. S. Pratap L. M. Kansal D. G. Saple Shatrughan Sahay Parag Kalyani Puneet Goyal Sharmila Patil A. J. Kanwar Bhavesh Swarnakar Sujay Kulkarni Abhijeet Morde Hitesh Khandagale Yogesh Dound Nitin Jadhav Sanjeev Hegde Murlidhara Padigaru Ashish C. Suthar Piramal Enterprises Limited Mumbai India Bhatia Skin Center Bima Nagar Indore India Agrawal Path LAB Vijaynagar Indore India Skin & Laser Center Krishna Nagar New Delhi India Diabetes and Shirdi Skin Care Centre Karnataka India Medipoint Hospitals Pvt. Ltd. Pentagon Research Pvt. Ltd. Pune India Skin Care Clinic Nagpur India NKP Salve Institute and Lata Mangeshkar Hospital Nagpur India Department of Dermatology Sheth VS General Hospital Ahmedabad India Sai Skin Care Clinic Hyderabad India Radiance Skin Care Clinic Nagpur India Dr. vikrant Saoji’s Clinic Ramdaspeth Nagpur India Durgabai Deshmukh Hospital & Research Center Hyderabad India Kansal Cosmetic & Skin Care Clinic Jaipur India Dr. Saple’s Clinic Dadar (East) Mumbai India Sri Skin Care & Laser Clinic Lucknow UP India Ruby Hall Clinic Pune India Renova Skin & Laser Clinic Sector-9 Mansarovar Jaipur India Dr. D. Y. Patil Medical College and Hospital Nerul Navi Mumbai India Department of Dermatology Venerology & Leprology Postgraduate Institute of Medical Education and Research Chandigarh India Swarnakar Superspeciality Centre Indore India Clinical Research and Development Piramal Enterprises Limited Mumbai India

Importance: This post-marketing surveillance study was conducted to evaluate real-world information about the efficacy and safety of oral Tinefcon? tablets (Sphaeranthus indicus based) in plaque psoriasis patients. Materials and Methods: Patients aged at least 18 years and older with clinical diagnosis of plaque psoriasis, were enrolled in this open label, non-comparative, multicenter trial. All eligible subjects received four 700 mg Tinefcon? tablets/day for 12 weeks. The primary outcome measure was percent change in Psoriasis Area Severity Index (PASI) score from baseline to week 12. The secondary outcome measures were Physician Global Assessment (PGA), Nail Psoriasis Severity Index (NAPSI), Psoriatic Arthritis Evaluation and Gene Expression Profiling and Immunohistochemistry. Results: After completion of Tinefcon? treatment at 12 weeks, more than half of subjects (52%) achieved PASI 50 response;PASI 75 response was attained in 68 (23%) subjects and PASI 90 response in 22 (7%) subjects. Five subjects with severe psoriasis achieved PASI 90 without receiving any concomitant medication. Reduction in severity as assessed by PGA was observed in more than half of patients with moderate disease. Histopathological evaluation revealed that epidermal thickness was considerably reduced in 66% of subjects. The expression of inflammatory marker S100A9 protein was(meaningfully reduced in 60% patients with non-significant reduction of Keratin 10 protein expression. Gene expression analysis showed increase down regulation of SERPINB4;PI3 and KRT16 genes after a 12-week treatment period in subjects with higher PASI scores. Conclusion: Oral Tinefcon? tablets showed good efficacy and had a favorable safety profile in plaque psoriasis patients.

关键词： Psoriasis Tinefcon® Tablet Sphaeranthus indicus

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