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Anthracycline-induced cardiotoxicity:A case report and review of literature

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World Journal of Cardiology 2021年第1期13卷 28-37页

作者： Esther G Chong Eric H Lee reena Sail Laura Denham Gayathri Nagaraj Chung-Tsen Hsueh Department of Medicine Loma Linda UniversityLoma LindaCA 92350United States Department of Hematology/Oncology Compassionate Cancer Care Medical GroupFountain ValleyCA 92708United States Department of Hematology/Oncology Scripps MD Anderson Cancer CenterSan DiegoCA 92121United States Department of Pathology and Human Anatomy Loma Linda UniversityLoma LindaCA 92350United States Division of Medical Oncology and Hematology Department of MedicineLoma Linda UniversityLoma LindaCA 92350United States

BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer *** use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart *** baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress *** underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment *** was evaluated regularly during chemotherapy without any cardiac or respiratory *** two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory *** showed an ejection fraction of 5%-10%with severe biventricular *** attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of *** autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity *** We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 *** monitoring and management of patients receivin

关键词： Anthracycline Cardiotoxicity Doxorubicin Troponin Brain natriuretic peptide Case report

hsa-mir-183 is frequently methylated and related to poor survival in human hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第9期23卷 1568-1575页

作者： Sumadi Lukman Anwar Till Krech Britta Hasemeier Elisa Schipper Nora Schweitzer Arndt Vogel Hans Kreipe reena Buurman Britta Skawran Ulrich Lehmann Ulrich Lehmann Institute of PathologyMedizinische Hochschule Hannover Department of Surgery Faculty of Medicine Universitas Gadjah Mada Department of Gastroenterology Hepatology and EndocrinologyMedizinische Hochschule Hannover Institute of Human Genetics Medizinische Hochschule Hannover

To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC).METHODSKnockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes. Quantification of DNA methylation and miRNA expression was then performed in primary HCC tumor samples and related with clinicopathological *** profiling after DNMT knockdown in HCC cell lines revealed upregulation of miR-23, miR-25 and miR-183. After qRT-PCR confirmation and CpG island methylation quantification of these miRNAs in cell lines, further analysis in primary HCC specimens showed that hsa-miR-183 is hypermethylated in 30% of HCC (n = 40). Expression of mature miR-183 showed an inverse correlation with DNA methylation levels. In HCC cells, DNMT knockdown and 5-aza-2’-deoxycytidine treatment reduced methylation and stimulated expression of miR-183. In HCC patients, hypermethylation at hsa-miR-183 promoter significantly correlates with poor survival (log-rank test P = 0.03). DNA methylation analysis in healthy liver, benign liver tumors (hepatocellular adenoma and focal nodular hyperplasia) and their corresponding adjacent tissues showed absence of hypermethylation supporting the notion that aberrant methylation at hsa-miR-183 is specific for the malignant transformation of *** data indicate that hypermethylation of hsa-miR-183 is a frequent event in HCC and potentially useful as a novel surrogate diagnostic and prognostic marker.

关键词： hsa-miR-183 DNA methylation DNMT knockdown microRNA microarray

A cAMP and CREB-mediated feed-forward mechanism regulates GSK3β in polycystic kidney disease

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Journal of Molecular Cell Biology 2016年第6期8卷 464-476页

作者： Vijayakumar R.Kakade Shixin Tao Madhumitha Rajagopal Xia Zhou Xiaogang Li Alan S.L.Yu James P.Calvet Pankaj Pandey reena Rao The Kidney Institute University of Kansas Medical CenterKansas CityKS 66160USA

Glycogen synthase kinase 3β(GSK3β),a serine/threonine protein kinase,is commonly known to be regulated at the level of its ***,in some diseases including polycystic kidney disease(PKD),GSK3βexpression is increased and plays a pathophysiological *** current studies aimed to determine the mechanism for the increased GSK3βexpression in PKD and its significance to disease *** mouse models of PKD,increases in renal GSK3βcorresponded with increases in renal cAMP levels and disease *** vivo and in vitro studies revealed that GSK3βis a cAMP-responsive gene,and elevated cAMP levels,as seen in PKD,can increase GSK3β*** normal mice,vasopressin signaling induced by water deprivation increased GSK3βexpression,which decreased following *** of the GSK3βpromoter revealed five potential binding sites for the transcription factor,cAMP response element binding protein(CREB).CREB was found to bind to GSK3βpromoter and essential for cAMP-mediated regulation of GSK3β.Importantly,this regulation was demonstrated to be part of a feedforward loop in which cAMP through CREB regulates GSK3βexpression,and GSK3βin turn positively regulates cAMP ***3βor CREB inhibition reduced transepithelial fluid secretion and cyst expansion in ***,disruption at any point of this destructive cycle may be therapeutically useful to reduce cyst expansion and preserve renal function in PKD.

关键词： GSK3β cAMP CREB in vitro cystogenesis PKD PKD1-knockout vasopressin

Prospective Development of Small Molecule Targets to Oncogenic Ras Proteins

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Open Journal of Biophysics 2013年第4期3卷 207-211页

作者： reena Chandrashekar Paul D. Adams Department of Chemistry and Biochemistry The University of Arkansas Fayetteville USA

Abnormal expression or mutations in Ras proteins has been found in up to 30% of cancer cell types, making them excellent protein models to probe structure-function relationships of cell-signaling processes that mediate cell transformtion. Yet, there has been very little development of therapies to help tackle Ras-related diseased states. The development of small molecules to target Ras proteins to potentially inhibit abnormal Ras-stimulated cell signaling has been conceptualized and some progress has been made over the last 16 or so years. Here, we briefly review studies characterizing Ras protein-small molecule interactions to show the importance and potential that these small molecules may have for Ras-related drug discovery. We summarize recent results, highlighting small molecules that can be directly targeted to Ras using Structure-Based Drug Design (SBDD) and Fragment-Based Lead Discovery (FBLD) methods. The inactivation of Ras oncogenic signaling in vitro by small molecules is currently an attractive hurdle to try to and leap over in order to attack the oncogenic state. In this regard, important features of previously characterized properties of small molecule Ras targets, as well as a current understanding of conformational and dynamics changes seen for Ras-related mutants, relative to wild type, must be taken into account as newer small molecule design strategies towards Ras are developed.

关键词： Ras [Rat Sarcoma] Small Molecule Target Structure-Based Drug Design Fragment-Based Drug Design GTP Hydrolysis Guanine Nucleotide Exchange Factors [GEF]

The Effect of Frat-1, Idax and Axam toward the Wnt Signaling Pathway

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Journal of Life Sciences 2011年第6期5卷 421-427页

作者： Nur Farahiyah Motiammad reena Peter Bruce Gardiner School of Mechatronic Universiti Malaysia Perlis Perlis Arau 02600 Malaysia Melbourne School of Engineering The University of Melbourne Melbourne Victoria 3010 Australia

This paper describes the effect of Frat-1, Idax and Axam toward the Wnt signaling pathway. The Wnt pathway is an important intracellular signaling pathway that plays a crucial role in the cell cycle process at several levels of development. Understanding this pathway thoroughly will enable identification of new drug targets and thereby open avenues to more effective therapies for a range of Wnt pathway related diseases such as cancer, osteoporosis, and mesothelioma. Dishevelled （Dsh） is one of the multi-module proteins working m the Wnt pathway. The function of Dsh depends on the regulators which bind to it, components it interacts with and most importantly the Wnt signal. It is important to note that positive regulators are those factors that induce gene transcription. Conversely, the negative regulators induce β-Catenin degradation. The positive regulator such as Frat- 1 would promote the Wnt signaling pathway and downstream gene transcription. Meanwhile the negative regulator such as Idax and Axam would inhibit the signaling pathway and promotes β-Catenin degradation which will thereby prevent aberrant gene transcription.

关键词： Wnt signaling cellular pathway regulators 13-catenin dishevelled.

Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India

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World Journal of Gastroenterology 2013年第22期19卷 3404-3414页

作者： reena Kumari Vineet Ahuja Jaishree Paul School of Life Sciences Jawaharlal Nehru University New Delhi 110067 India Department of Gastroenterology All India Institute of Medical Sciences New Delhi 110029 India

AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 control individuals (hemorrhoid patients only) and 26 UC patients (severe: n = 12, moderate: n = 6, remission: n = 8), recruited by the gastroenterologist at the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Disease activity in UC patients was determined by clinical colitis activity index. We employed fluorescent in situ hybridization in combination with flow cytometry to enumerate the clostridium cluster population targeted by 16S rRNA gene probe. Major butyrate-producing species within this cluster were quantified to see if any change existed in control vs UC patients with different disease activity. This observed change was further validated by quantitative polymerase chain reaction. In addition to this,we carried out gas chromatography to evaluate the changes in concentration of major short chain fatty acids (SCFAs), namely acetate, n -butyrate, iso -butyrate, in the above samples. Student t test and Graph pad prism-6 were used to compare the data statistically. RESULTS: There was a significant decrease of Clostridium coccoides (control, 25.69% ± 1.62% vs severe, 9.8% ± 2.4%, P = 0.0001) and Clostridium leptum clusters (control, 13.74% ± 1.05% vs severe, 6.2% ± 1.8%, P = 0.0001) in fecal samples of UC patients. Furthermore, we demonstrated that some butyrateproducing members of the clostridial cluster, like Fecalibacterium prausnitzii (control, 11.66% ± 1.55% vs severe, 6.01% ± 1.6%, P = 0.0001) and Roseburia intestinalis (control, 14.48% ± 1.52% vs severe, 9% ± 1.83%, P = 0.02) were differentially present in patients with different disease activity. In addition, we also demonstrated decreased concentrations of fecal SCFAs, especially of n -butyrate (control, 24.32 ± 1.86 mmol/μL vs severe, 12.74 ± 2.75 mmol

关键词： Fecal microbiota Ulcerative colitis Short chain fatty acids Clostridial cluster Fluorescent in situ hybridization-flow cytometry Quantitative polymerase chain reaction

Alteration in the expression of microRNA-21 regulated target genes:Role in breast cancer

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BIOCELL 2022年第2期46卷 309-324页

作者： PRIYANKA THAKUR reena V.SAINI ANIL K.CHHILLAR NEERAJ K.SAINI VIJAY KUMAR THAKUR SAMARJEET SINGH SIWAL ADESH K.SAINI Faculty of Sciences Shoolini UniversitySolan173229India Department of Biotechnology MMECMaharishi Markandeshwar(Deemed to be University)Ambala133207India Maharishi Markandeshwar University Solan173229India Centre of Biotechnology Maharshi Dayanand UniversityRohtak124001India School of Biotechnology Jawaharlal Nehu UniversityNew Delhi110067India Biorefining and Advanced Materials Research Center Scotland’s Rural College(SRUC)EdinburghEH93JGUK Department of Chemistry MMECMaharishi Markandeshwar(Deemed to be University)Ambala133207India

Breast cancer,also recognized as the principal cause of cancer-related deaths among women,is the second most familiar and prevalent form of *** diagnostic and prognostic biomarkers that are highly specific are urgently needed for its early ***(miRNAs),a class of non-coding RNAs,are known to control the biological processes involving transcription,post-transcriptional and covalent modifications,splicing,translation,cell differentiation,proliferation,apoptosis,cancer progression,and *** dysregulation in miRNA expression,demonstrating their oncogenic and tumor-suppressive functions,contributes to cancer ***-21(miR-21),an‘onco-miR’in breast cancer,is involved in tumor progression and metastasis by suppressing the activity of the target gene via its interaction with the 3’UTR of the target *** upregulation of miR-21 is observed in many instances of breast *** review aims to summarize the current understanding of miR-21 in the regulation of important cellular functions via regulation of its target *** discuss its biosynthesis,oncogenic function in breast cancer,and different methods used for its *** will increase the current understanding of the role of miR-21 in breast cancer tumorigenesis,which will offer a perception of using miR-21 as an early detection molecular prognostic and diagnostic biomarker and as a therapeutic target in breast cancer care.

关键词： Non-coding RNA microRNAs Breast cancer Tumor suppression Biomarker

Role of Complements and Immunoglobulins in Duchenne Muscular Dystrophy

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Open Journal of Applied Sciences 2014年第6期4卷 323-346页

作者： Sanjeev Kumar reena Mittal Sweety &nbsp Depp Chand Jain Department of Mathematics Shri.K.K.JAIN. College Khatauli India Department of Neurology Safdarganj Hospital New Delhi India Department of Physics Central Medical Physics Research Laboratory D.A.V. (P.G.) College Muzaffarnagar India

Muscular dystrophies are myopathies and tend to progressive, with ongoing degeneration and regeneration of muscle fibers. Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and polio myelitis are essentially diseases of the anterior horn cells of the spine. It has been reported in literature that humoral immunity is manifested by the antibodies production. These are special chemical substances that react against foreign body. Antibodies are serum proteins, which are immunoglobulins and possess antibody activity and are classified according to antigens and stimulate their production such as IgA, JgG, IgM, IgD and IgE. All the immunological parameters such as of C3, C4, IgG, IgM and IgA, which are measured in Duchenne muscular dystrophy go down in comparison to healthy subjects. Complement C3 and Complement C4 go down about 44.3% and 78.57% respectively from the normal values. The serum IgG, IgM and IgA levels were also go down about 65%, 84% and 99.56% respectively in comparison to healthy subjects. A trend between all the immunoglobulins has been set up and it is rAG.M > rMA.G. > rGM.A, while we have a trend in DMD cases is rMA.G. > rAG.M > rGM.A We are in a position to say that our data have a relevance of high authenticity and reliability to accept that there is a deficit in immunity in DMD cases. The deficit in immunity may be a cause to damage muscle for abnormal functioning.

关键词： Complements Immunoglobulins Duchenne Muscular Dystrophy Regression Coefficients Multiple Correlation Coefficients

Electrochemical Synthesis of Novel Zn-Doped TiO_2 Nanotube/ZnO Nanoflake Heterostructure with Enhanced DSSC Efficiency

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Nano-Micro Letters 2016年第4期8卷 381-387页

作者： Aijo John K Johns Naduvath Sudhanshu Mallick Jacob W.Pledger S.K.Remillard P.A.De Young Manju Thankamoniamma T.Shripathi Rachel reena Philip Department of Physics Union Christian College Department of Metallurgical Engineering and Material Science Indian Institute of Technology Present Address Department of Physics St.Thomas College Department of Physics Hope College Department of Physics Sree Sankara College UGC-DAE Consortium for Scientific Research Indore

The paper reports the fabrication of Zn-doped TiO_2 nanotubes(Zn-TONT)/ZnO nanoflakes heterostructure for the first time,which shows improved performance as a photoanode in dye-sensitized solar cell(DSSC).The layered structure of this novel nanoporous structure has been analyzed unambiguously by Rutherford backscattering spectroscopy,scanning electron microscopy,and X-ray *** cell using the heterostructure as photoanode manifests an enhancement of about an order in the magnitude of the short circuit current and a seven-fold increase in efficiency,over pure TiO_2 *** further reveal that the Zn-TONT is preferentially oriented in [001] direction and there is a Ti metal-depleted interface layer which leads to better band alignment in DSSC.

关键词： Zn-doped TiO2 nanotubes ZnO nanoflakes Heterostructures DSSC