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Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma

World Journal of Clinical Oncology 2019年第3期10卷 149-160页

作者： Jennifer Wu Merly Contratto Krishna P Shanbhogue gulam a manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee Division of Hematology and Oncology Perlmutter Cancer CenterNew York University School of Medicine Department of Radiology at New York University School of Medicine Division of Hematology and Oncology Columbia University Medical Center Division of Hematology and Oncology Indiana University Division of Hematology and Oncology Ohio State University Medical Center Roche Pharmaceutical Company Roche and Teclison Pharmaceutical Company

BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in *** To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to *** In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of *** Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased *** study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes

关键词： Hepatocellular carcinoma Hypoxia-inducible factor 1α RO7070179,Superresponder Dynamic contrast-enhanced-magnetic resonance imaging

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LMI Consensus Condition for Discrete-time Multi-agent Systems

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IEEE/CAA Journal of Automatica Sinica 2018年第2期5卷 509-513页

作者： Magdi S.Mahmoud gulam Dastagir Khan Systems Engineering Department KFUPM E O. Box 5067 Dhahran 31261 Saudi Arabia

This paper examines a consensus problem in multiagent discrete-time systems, where each agent can exchange information only from its neighbor agents. A decentralized protocol is designed for each agent to steer all agents to the same vector. The design condition is expressed in the form of a linear matrix inequality. Finally, a simulation example is presented and a comparison is made to demonstrate the effectiveness of the developed methodology.

关键词： Index Terms-Consensus algorithms discrete-time systems linear matrix inequalities multi-agent systems.

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Hepatitis C virus NS5A promotes insulin resistance through IRS-1 serine phosphorylation and increased gluconeogenesis

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World Journal of Gastroenterology 2015年第43期21卷 12361-12369页

作者： Fahed Parvaiz Sobia Manzoor Jawed Iqbal Mehuli Sarkar-Dutta Muhammad Imran gulam Waris Atta-urRahman School of Applied Biosciences National University of Sciences and Technology Department of Microbiology and Immunology Rosalind Franklin University of Medicine and Science

AIM: To investigate the mechanisms of insulin resistance in human hepatoma cells expressing hepatitis C virus(HCV) nonstructural protein 5A(NS5A).METHODS: The human hepatoma cell lines,Huh7 and Huh7.5,were infected with HCV or transientlytransfected with a vector expressing HCV NS5 A. The effect of HCV NS5 A on the status of the critical players involved in insulin signaling was analyzed using realtime quantitative polymerase chain reaction and Western blot assays. Data were analyzed using Graph Pad Prism version ***: To investigate the effect of insulin treatment on the players involved in insulin signaling pathway,we analyzed the status of insulin receptor substrate-1(IRS-1) phosphorylation in HCV infected cells or Huh7.5 cells transfected with an HCV NS5 A expression vector. Our results indicated that there was an increased phosphorylation of IRS-1(Ser307) in HCV infected or NS5 A transfected Huh7.5 cells compared to their respective controls. Furthermore,an increased phosphorylation of Akt(Ser473) was observed in HCV infected and NS5 A transfected cells compared to their mock infected cells. In contrast,we observed decreased phosphorylation of Akt Thr308 phosphorylation in HCV NS5 A transfected cells. These results suggest that Huh7.5 cells either infected with HCV or ectopically expressing HCV NS5 A alone have the potential to induce insulin resistance by the phosphorylation of IRS-1 at serine residue(Ser307) followed by decreased phosphorylation of Akt Thr308,Fox01 Ser256 and GSK3β Ser9,the downstream players of the insulin signalingpathway. Furthermore,increased expression of PECK and glucose-6-phosphatase,the molecules involved in gluconeogenesis,in HCV NS5 A transfected cells was ***: Taken together,our results suggest the role of HCV NS5 A in the induction of insulin resistance by modulating various cellular targets involved in the insulin signaling pathway.

关键词： Hepatitis C virus nonstructural protein 5A Insulin

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Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1

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World Journal of Gastroenterology 2017年第36期23卷 6639-6649页

作者： Yirui Gui Md gulam Musawwir Khan Diwakar Bobbala Claire Dubois Sheela Ramanathan Caroline Saucier Subburaj Ilangumaran Department of Pediatrics Immunology DivisionFaculty of Medicine and Health SciencesUniversity of Sherbrooke Department of Anatomy and Cell Biology Faculty of Medicine and Health SciencesUniversitéde Sherbrooke

AIM To investigate the role of suppressor of cytokine signaling 1(SOCS1)in regulating MET-mediated invasive potential of hepatocellular carcinoma(HCC)*** derivatives of mouse(Hepa1-6)and human(hep3B,Hep G2)HCC cell lines expressing SOCS1or control vector were evaluated for their ability to migrate towards hepatocyte growth factor(HGF)in the transwell migration assay,invade extracellular matrix in response to HGF stimulation in a 3-D invasion assay by confocal microscopy,and to undergo anchorageindependent proliferation in semisolid *** intravenous and intrasplenic inoculation into *** mice,the ability of Hepa cells to form othotopic tumors was *** HGF stimulation of Hepa and Hep3B cells,expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qR *** SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through *** the 3-D invasion assay,HGF stimulation induced invasion of HCC cells across type-Ⅰcollagen matrix,and SOCS1expression significantly reduced the depth of ***1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid *** intravenous inoculation,control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller *** formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein *** stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1,SNAI1and *** results were obtained with Hep3B ***1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 *** Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated m

关键词： Migration Invasion MET Hepatocellular carcinoma Suppressor of cytokine signaling 1

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Toward point-of-care assessment of patient response:a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning

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Microsystems & Nanoengineering 2019年第1期5卷 333-343页

作者： Karan Ahuja gulam M.Rather Zhongtian Lin Jianye Sui Pengfei Xie Tuan Le Joseph R.Bertino Mehdi Javanmard Department of Electrical and Computer Engineering Rutgers UniversityNew BrunswickNJUSA Rutgers Cancer Institute of New Jersey Rutgers UniversityNew BrunswickNJUSA

We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor *** have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification *** commercially available devices for the automated analysis of cell viability are based on staining,which fundamentally limits the subsequent characterization of these cells as well as downstream molecular *** approach requires as little as 20μL of volume and avoids staining allowing for further downstream molecular *** the best of our knowledge,this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning,particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier,to assess viability of cells without staining or labelling.

关键词： assessing impedance drugs

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Rural-urban differences in distributions and determinants of facility delivery among women in Bangladesh

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Global Health Journal 2023年第4期7卷 222-229页

作者： Jannatun Nayeem Christina Stennett Atia Sharmeen Md Mahbub Hossain gulam Muhammed Al Kibria Comilla Medical College Comilla 3500Bangladesh University of Maryland School of Medicine BaltimoreMD 21201United States Morgan State University BaltimoreMD 21093United States Texas A&M School of Public Health College StationTexasTX 77843United States Johns Hopkins Bloomberg School of Public Health BaltimoreMD 21205United States

Introduction:The utilization of facility delivery is crucial to achieve sustainable development goals by reducing maternal and neonatal *** study aimed to compare the distributions and determinants of childbirth in health facilities in urban and rural regions of ***:Cross-sectional data from the 2017-2018 Bangladesh Demographic and Health Survey were *** logistic regression was ***:A total of 4751 women were included in the *** 50%of childbirths took place in health facilities,63.4%and 44.6%in urban and rural regions,***,the odds of the association between facility delivery and the studied factors were *** women had significantly lower odds of facility delivery in both rural(adjusted odds ratio[AOR]=0.3,95%confidence interval[CI]:0.2 to 0.5)and urban(AOR=0.2,95%CI:0.1 to 0.5)*** both regions,women with higher education levels,highly educated husbands,antenatal care(ANC),and higher wealth indexes had significantly higher odds of facility ***:Several common associated factors were ***,differences were observed regarding distributions of these *** differences in facility delivery utilization could result from lower ANC utilization,socioeconomic status,and transportation facilities in rural regions than urban regions;therefore,improving these conditions could increase facility delivery in these regions.

关键词： Bangladesh Facilitydelivery Determinants Distributions Urban Rural Childbirth

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Prevalence and factors associated with underweight,overweight and obesity among women of reproductive age in India

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Global Health Research and Policy 2019年第1期4卷 115-126页

作者： gulam Muhammed Al Kibria Krystal Swasey Md Zabir Hasan Atia Sharmeen Brendan Day Department of Epidemiology and Public Health University of Maryland School of Medicine655 West Baltimore StreetBaltimore MD-21201USA Department of International Health Johns Hopkins Bloomberg School of Public HealthBaltimore MD-21205USA School of Community Health and Policy Morgan State UniversityBaltimore MD-21251USA

Introduction:Although the prevalence of underweight is declining among Indian women,the prevalence of overweight/obesity is *** study examined the prevalence and factors associated with underweight and overweight/obesity among reproductive-aged(i.e.,15-49 years)women in ***:This cross-sectional study analyzed data from the 2015-16 National Family Health *** Asian and World Health Organization(WHO)recommended cutoffs for body mass index(BMI)were used to categorize body *** Asian and WHO BMI cutoffs for combined overweight/obesity were≥23 and≥25 kg/m2,*** recommendations had the same cutoff for underweight,<18.5 kg/*** prevalence estimation,logistic regression was applied to investigate associated ***:Among 647,168 women,the median age and BMI was 30 years and 21.0 kg/m2,*** on the Asian cutoffs,the overall prevalence of underweight was 22.9%,overweight was 22.6%,and obesity was 10.7%,compared to 15.5%overweight and 5.1%obesity as per WHO *** prevalence and odds of underweight were higher among young,nulliparous,contraceptive non-user,never-married,Hindu,backward castes,less educated,less wealthy,and rural *** to both cutoffs,women who were older,ever-pregnant,evermarried,Muslims,castes other than backwards,highly educated,wealthy,and living in urban regions had higher prevalence and odds of overweight/***:The prevalence of both non-normal weight categories(i.e.,underweight and overweight/obesity)was high.A large proportion of women are possibly at higher risks of cardiovascular and reproductive adverse events due to these double nutrition *** large-scale interventions based on these results is essential to address these issues.

关键词： Body weight Underweight Overweight Obesity India Prevalence Factor Correlate Body mass index Prevalence Women

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中国苏州人群住院患儿博卡病毒与混合感染引起的下呼吸道感染比较研究

中国苏州人群住院患儿博卡病毒与混合感染引起的下呼吸道感染比较...

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作者： Mohammed gulam Subhani 苏州大学

学位级别：硕士

目的:最近发现的细小病毒人类博卡病毒(HBoV)在儿童呼吸道感染(LRTI)中占有重要的地位。然而其发病率,作为单一和混合病毒感染在呼吸道疾病的的作用尚无定论。本研究的目的是研究和比较住院儿童下呼吸道感染(LRTI)中HBoV单一和混合病毒... 详细信息

目的:最近发现的细小病毒人类博卡病毒(HBoV)在儿童呼吸道感染(LRTI)中占有重要的地位。然而其发病率,作为单一和混合病毒感染在呼吸道疾病的的作用尚无定论。本研究的目的是研究和比较住院儿童下呼吸道感染(LRTI)中HBoV单一和混合病毒感染的临床特点。方法:回顾性分析2013年1月至2016年12月在苏州大学附属儿童医院呼吸科就诊的513例感染患儿。比较HBoV单一感染和混合感染有关的临床数据。鼻咽抽吸物病毒检测通过免疫荧光测定或聚合酶链式反应(PCR)检查。结果:在本研究中,对LRTI患者进行了 HBoV感染筛查,并将其分为单一病毒和混合病毒感染。1.在 8213 例 LRTI 患儿中,513 例(6.24%)HBoV 阳性。2.在HBoV感染的513名患者中,329名(64.13%)是男性,184名(35.87%)是女性。男女比例为1.78:1。3.中位年龄为13个月(范围从1个月到16岁)。年龄在6-24个月的年龄组中的病例数最高。在513名HBoV患者中,有292名患者的年龄在6-24个月之间,占56.9%,而在大于或等于60个月的年龄组中,比例最低为2.92%(15名)。4.在小于或等于12个月和～24个月的年龄组中观察到比例最高,分别占140例,27.2%和152例,29.6%。在～36个月的年龄组中有67例占13.06%,～60个月年龄组中52个病例占10.13%。***感染全年散发,但多数发生在冬季和秋季。我们的研究还报道了 HBoV感染在2015年呈爆发流行,发生率高于2013年,2014年和2016年。6.513例HBoV感染的患者中,冬季感染病例66例(12.8%),春季115 例(22.4%);夏季 150 例(29.23%),秋季 173 例(33.72%)。303例单纯HBoV感染中,冬季45例(14.9%);春季63例,(20.8%);夏季86(28.7%),秋季109例(36.0%),210例混合型病毒感染患者中,冬季20例,占9.50%;春季47例(22.4%);夏季71例(33.8%),秋季 72 例(34.3%)。7.513例中有210例(40.9%)混合感染患儿,49.6%<6月龄患者合并感染,6个月至<1岁患者为45.4%,1至<2岁患者为35.3%,2至<5岁患者为37.3%,31.9%的患者≥5岁。8.在混合感染210例患者中,常见的病原体为RSV(14.8%),HRV(26.87%),肺炎支原体(24.63%),PIV(5.97.6%)和其他(4.48%),9.混合病毒感染患者组中发烧儿童的比例较高。单一病毒感染的儿童的中位年龄(13个月)与感染混合病毒的儿童的中位年龄(12个月)相似。入院前抗生素的使用时间和使用情况在两组患者中没有显着差异。10.单个病毒感染组患儿血液样本中,平均外周血白细胞计数为8.9×10^9/L,粒细胞平均百分比为43.8%,淋巴细胞为42.85%,平均血小板水平为337.2,肌酸激酶心肌酶(CKMB)为68.43 ng/mL。而在混合病毒组中,平均外周血白细胞计数为11.97×10^9/L,粒细胞平均百分比为44.8%,淋巴细胞为39.02%,平均血小板水平为332.2,CKMB 为 26.04 ng/mL。11.我们的研究注意到两组间IgA,IgG和IgM水平的统计学差异。在混合病毒感染的情况下,发现免疫球蛋白G水平显着更高(p<0.01),而单个病毒组中的免疫球蛋白A水平更高(p<0.01)。然而,两组之间的免疫球蛋白M值没有显着差异。12.在肝功能测试中,单病毒感染患者的平均丙氨酸转氨酶(ALT)水平为34.79U/L,平均天冬氨酸转氨酶(AST)水平为19.18U/L。而混合病毒感染患者的平均ALT水平为26.52 U/L,平均AST水平为37.65 U/L。与单一病毒感染患者相比,混合病毒感染患者的AST水平显着升高。13.两组患儿在 CD3+,CD3 + CD4+,CD3-CD8+,CD4/CD8,CD3-CD19 +,CD3-CD(16 + 56)+ 和 CD19 + CD23 + 中没有发现显着性统计学差异。结论:在呼吸道感染中,HBoV病毒混合感染比例较高,与单一感染相比,混合感染组患儿在人口统计学和临床特征无显着差异。因LRTI住院人群中HBoV病毒感染率较高,表明需要增强敏感,廉价和快速的诊断以准确识别下呼吸道病原体。

关键词：肺炎人类博卡病毒单一病毒感染混合病毒感染病毒合并感染下呼吸道感染

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Denoising of Medical Images Using Multiwavelet Transforms and Various Thresholding Techniques

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Journal of Signal and Information Processing 2013年第1期4卷 24-32页

作者： Abdullah Al Jumah Mohammed gulam Ahamad Syed Amjad Ali Department of Computer Engineering College of Computer Engineering & Science Salman bin Abdulaziz University Al-Kharj Saudi Arabia Department of Electronics & Communication Engineering Lords Institute of Engineering & Technology Hyderabad India

The problem of estimating an image corrupted by additive white Gaussian noise has been of interest for practical reasons. Non-linear denoising methods based on wavelets, have become popular but Multiwavelets outperform wavelets in image denoising. Multiwavelets are wavelets with several scaling and wavelet functions, offer simultaneously Orthogonality, Symmetry, Short support and Vanishing moments, which is not possible with ordinary (scalar) wavelets. These properties make Multiwavelets promising for image processing applications, such as image denoising. The aim of this paper is to apply various non-linear thresholding techniques such as hard, soft, universal, modified universal, fixed and multivariate thresholding in Multiwavelet transform domain such as Discrete Multiwavelet Transform, Symmetric Asymmetric (SA4), Chui Lian (CL), and Bi-Hermite (Bih52S) for different Multiwavelets at different levels, to denoise an image and determine the best one out of it. The performance of denoising algorithms and various thresholding are measured using quantitative performance measures such as, Mean Square Error (MSE), and Root Mean Square Error (RMSE), Signal-to-Noise Ratio (SNR), Peak Signal-to-Noise Ratio (PSNR). It is found that CL Multiwavelet transform in combination with modified universal thresholding has given best results.

关键词： Multiwavelets Noise Thresholding Additive White Gaussian Noise Signal-to-Noise Ratio Discrete Multiwavelet Transforms Chui Lian Symmetric Asymmetric Multiwavelet Transform Bi-Hermite Multiwavelet Transform Modified Universal Thresholding

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Predictive Analysis on Hypertension Treatment using Data Mining Approach in Saudi Arabia

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Intelligent Information Management 2011年第6期3卷 252-261页

作者： Abdullah A. Aljumah Mohammed gulam Ahamad Mohammad Khubeb Siddiqui College of Computer Engineering and Sciences Salman bin Abdulaziz University

In the present investigation, the data sets of (Non Communicable Diseases) NCD risk factors a standard report of Saudi Arabia 2005 in collaboration with World Health Organisation have been employed for regression analysis using data mining technique and that leads to the prediction of which treatment contributes more to improvement in hypertension. The Oracle Data Miner (ODM) tool has been used for the analysis of data. The data sets for different age groups in case of blood pressure treatment for hypertension for Male using different modes have been studied. The age group is in between of 15 years to 64 years. Data mining is an appropriate and sufficiently sensitive method to analyze outcomes of which mode of treatment is more effective to which age group. The Oracle data miner predicts the best mode of treatment for each group by which one can analyse the appropriate treatment. The predictions are also been compared with the help of residual plots. The residual graphs have been correlated with the predictions.

关键词： Hypertension Data Mining Regression Residual Plots Prediction

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