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Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

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Cancer Drug Resistance 2019年第2期2卷 271-296页

作者： heidi schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06126Italy

Initially,most ovarian tumors respond to the treatment with platinum components,but frequently recurrence occurs within the following two years in advanced ovarian cancer *** this regard,previous studies have shown changes in the epigenetic patterns in ovarian cancer that are linked with resistance to cis-and carboplatin ***,epigenetic changes mediated by a treatment with cis-or carboplatin could identify such patients who do or do not respond to this ***,an understanding of the impact of platinum on epigenetics in ovarian cancer is important in overcoming platinum *** this review,we delineate epigenetic abnormalities in cis-and carboplatin-resistant ovarian tumors,such as changes in DNA methylation,histone modifications and deregulation of microRNAs,and discuss the potential of epigenetic therapies in combination with platinum.

关键词： Ovarian cancer carboplatin cisplatin resistance DNA methylation histone modifications microRNAs

Circulating non-coding RNAs in recurrent and metastatic ovarian cancer

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Cancer Drug Resistance 2019年第3期2卷 399-418页

作者： heidi schwarzenbach Peter B.Gahan Department of Tumor Biology University Medical Center Hamburg-EppendorfHamburg 20246Germany Fondazione“Enrico Puccinelli”Onlus Perugia 06123Italy

Ovarian cancer has a poor outcome because it is usually detected at advanced tumor stages,and the majority of the patients develop disease relapse as a result of chemotherapy *** most lethal gynecological malignancy metastasizes within the peritoneal fluid or ascites to pelvic and distal *** ovarian cancer progression and metastasis,small non-coding RNAs(ncRNAs),including long noncoding RNAs and microRNAs have been recognized as important *** dysregulation modulates gene expression and cellular signal pathways and can be detected in liquid *** this review,we provide an overview on circulating plasma and serum ncRNAs participating in tumor cell migration and invasion,and contributing to recurrence and metastasis of ovarian *** will also discuss the development of potential,novel therapies using ncRNAs as target molecules or tumor markers for ovarian cancer.

关键词： Ovarian cancer recurrence metastasis epithelial-mesemchmal transition non-coding RNAs chemotherapy tumor markers

Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients

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World Journal of Gastroenterology 2006年第33期12卷 5352-5356页

作者： Viacheslav N Kalinin Jussuf T Kaifi heidi schwarzenbach Anatoly S Sergeyev Bjoern C Link Dean Bogoevski Yogesh Vashist Jakob R Izbicki Emre F Yekebas Department of General Visceral and Thoracic Surgery University Medical Center Hamburg-Eppendorf Hamburg Germany Institute for Tumor Biology University Medical Center Hamburg-Eppendorf Hamburg Germany Research Centre for Medical Genetics Moscow Russia

AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis. METHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms, and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specifi c PCR and DNA sequencing. RESULTS: The most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS) 3 + 2 T > C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5’untranslated region (UTR)-215 G > A. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 ***: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 T > C SPINK1 gene mutation and a base substitution 5’UTR-215 G > A inthe same gene copy. Most probably the 5’UTR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 T > C mutation in thesepatients.

关键词： Chronic pancreatitis Serine protease inhibitor Kazal type 1 Gene mutations

Photobiomodulation:a novel approach to promote trans-differentiation of adipose-derived stem cells into neuronal-like cells

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Neural Regeneration Research 2025年第2期20卷 598-608页

作者： Daniella Da Silva Madeleen Jansen van Rensburg Anine Crous heidi Abrahamse Laser Research Centre Faculty of Health SciencesUniversity of JohannesburgDoornfonteinJohannesburgSouth Africa

Photobiomodulation,originally used red and near-infrared lasers,can alter cellular *** has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of *** this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain *** investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/*** adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory *** findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control ***,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal *** biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic ***,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.

关键词： differentiation inducers green photobiomodulation immortalized adipose-derived stem cell near-infrared photobiomodulation neurodegenerative disease neurogenesis photobiomodulation trans-differentiation

Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon J.Brown Rafael J.Yáñez-Muñoz heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1077-1097页

作者： Lindokuhle Cindy Nene heidi Abrahamse Laser Research Centre Faculty of Health SciencesUniversity of JohannesburgDoornfontein 2028South Africa

Cancer remains one of the diseases with the highest incidence and mortality *** treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and ***-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic *** combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer *** use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and *** review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

关键词： Sonodynamic therapy Photodynamic therapy Combinatorial therapy Phthalocyanines Sensitizer Cancer

Ecohydrological processes and ecosystem services in the Anthropocene: a review

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Ecological Processes 2017年第1期6卷 364-372页

作者： Ge Sun Dennis Hallema heidi Asbjornsen Eastern Forest Environmental Threat Assessment Center Southern Research StationU.S.Department of Agriculture Forest Service920 Main Campus Dr.Suite 300RaleighNC 27606USA Oak Ridge Institute for Science and Education U.S.Department of EnergyOak RidgeTN 37830USA Institute for the Study of Earth Oceansand SpaceUniversity of New HampshireDurhamNHUSA

The framework for ecosystem services has been increasingly used in integrated watershed ecosystem management practices that involve scientists,engineers,managers,and policy *** objective of this review is to explore the intimate connections between ecohydrological processes and water-related ecosystem services in human-dominated ecosystems in the *** synthesize current literature to illustrate the importance of understanding the ecohydrological processes for accurately quantifying ecosystem services under different environmental and socioeconomic settings and *** synthesis focuses on managed ecosystems that are dominated by humans and explores how ecological processes affect the tradeoffs and synergies of multiple ecosystem *** identify research gaps in studying ecological processes mainly including energy,carbon,water,and nutrient balances to better assess and quantify ecosystem services that are critical for sustaining natural resources for future *** better assess ecosystem services,future ecohydrological studies need to better account for the scaling effects of natural and anthropogenic stressors exerted on evapotranspiration and other water supply and demand *** studies should focus on the bidirectional interactions between hydrological functions and services and human actions to solve real world problems such as water shortages,ecological degradation,and climate change adaptation.

关键词： watershed services ecosystem

Spatial context in the calculation of gas emissions for underground coal mines

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International Journal of Mining Science and Technology 2017年第5期27卷 787-794页

作者： Patrick Booth heidi Brown Jan Nemcik Ren Ting School of Civil Mining and Environmental EngineeringSchool of Earth and Environmental SciencesUniversity of WollongongWollongong 2500Australia

The prediction of gas emissions arising from underground coal mining has been the subject of extensive research for several decades, however calculation techniques remain empirically based and are hence limited to the origin of calculation in both application and resolution. Quantification and management of risk associated with sudden gas release during mining(outbursts) and accumulation of noxious or combustible gases within the mining environment is reliant on such predictions, and unexplained variation correctly requires conservative management practices in response to risk. Over 2500 gas core samples from two southern Sydney basin mines producing metallurgical coal from the Bulli seam have been analysed in various geospatial context including relationships to hydrological features and geological structures. The results suggest variability and limitations associated with the present traditional approaches to gas emission prediction and design of gas management practices may be addressed using predictions derived from improved spatial datasets, and analysis techniques incorporating fundamental physical and energy related principles.

关键词： Gas emission prediction Spatial analysis Underground coal mining Risk management Greenhouse gas Climate

The Shifting Landscape of Latent Print Testimony:An American Perspective

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Journal of Forensic Science and Medicine 2017年第2期3卷 72-81页

作者： heidi Eldridge RTI International Research Triangle ParkNCUSA School of Criminal Justice University of LausanneLausanneSwitzeriand

Friction ridge comparison testimony in the United States has long been characterized by speaking in absolutes:fingerprints are unique,the Analysis,Comparison,Evaluation,and Verification methodology has a zero-error rate,and the testimony presented by the expert should be regarded as an incontrovertible *** the National Research Council released their watershed report in 2009,questioning and criticizing these clear overstatements of the strength of the evidence,many commentators and professional organizations recommended that the friction ridge community rethink the way their evidence was presented in reports and in ***,change has been slow to *** some agencies have begun a shift in the way they present their findings,many others still testify the same way they always *** paper presents the historical context of where American friction ridge testimony has been,lays out the arguments for why it needs to change,describes some recent efforts to improve,and highlights some likely directions for the future of friction ridge reporting and testimony in the United States.

关键词： Friction ridge latent prints testimony