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Clinical variability and molecular heterogeneity inprostate cancer

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Asian Journal of Andrology 2016年第4期18卷 543-548页

作者： Jonathan Shoag Christopher E Barbieri Department of Urology NewYork-Presbyterian Hospital Weill Cornell Medical College New York USA sandra and edward meyer cancer center Weill Cornell Medica College New York USA.

Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care.

关键词： cell biology ERG genomics molecular heterogeneity prostate cancer sequencing serine peptidase inhibitor, Kazaltype 1 SPOP tumor profiling

Quantitative analysis of taxane drug target engagement of microtubules in circulating tumor cells from metastatic castration resistant prostate cancer patients treated with CRXL301,a nanoparticle of docetaxel

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cancer Drug Resistance 2020年第3期3卷 636-646页

作者： Eiman Mukhtar Daniel Worroll Giuseppe Galletti Shelly Schuster Sarina A.Piha-Paul Paraskevi Giannakakou Department of Medicine Hematology/OncologyWeill Cornell MedicineNew YorkNY 10065USA. sandra and edward meyer cancer center Department of MedicineWeill Cornell MedicineNew YorkNY 10065USA. NewLink Genetics Corporation AmesIA 50010USA. The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA.

Aim:We reviewed the radiographic response of three patients with metastatic castration-resistant prostate cancer treated with CRXL301,a docetaxel *** these three patients,we isolated and analyzed circulating tumor cells(CTCs)to explore microtubule(MT)drug-target engagement(MT-DTE)as a biomarker of response to ***-DTE was based on a quantitative assessment of the MT cytoskeleton in CTCs from pre-and posttreatment patient samples as a potential read-out of CRXL301 ***:We isolated CTCs using negative CD45+depletion and subjected them to multiplex confocal microscopy using our established *** were identified as CD45-/CK+/DAPI+cells and MT-DTE was determined using our developed imaging *** quantified MT bundling in CTCs across multiple time points,from baseline to on-treatment to disease ***,we describe the longitudinal analysis of MT-DTE in CTCs from patients treated with CRXL301 and its correlation with response to ***:We collected CTCs at seven time points from three metastatic castration-resistant prostate cancer *** response was evaluated by Response Evaluation Criteria in Solid Tumors(RECIST)v.1.1 criteria in those patients with measurable *** the three patients enrolled,one experienced partial response(-50%)to CRXL301 and two patients were unevaluable given bone only ***,however,these two patients showed stable disease clinically based on bone ***-DTE across all time points revealed that,early time points within four and 24 h of drug administration exhibited the highest levels of drug engagement(MT-DTE)as compared to ***,these early time points did not correlate with clinical *** observed that the CTCs collected one week after the first or second dose of CRXL301 treatment in the responding patient had numerically higher levels of MT-DTE as compared to the other two ***:Taxane on-target activity can be detected

关键词： Liquid biopsy circulating tumor cells castration-resistant prostate cancer microtubules taxanes biomarkers

Using circulating tumor cells to advance precision medicine in prostate cancer

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Journal of cancer Metastasis and Treatment 2017年第1期3卷 190-205页

作者： Giuseppe Galletti Daniel Worroll David M.Nanus Paraskevi Giannakakou Department of Medicine Hematology and OncologyWeill Cornell MedicineNew YorkNY 10065USA sandra and edward meyer cancer center Department of MedicineWeill Cornell MedicineNew YorkNY 10065USA.

The field of circulating tumor cell(CTC)enrichment has seen many emerging technologies in recent years,which have resulted in the identification and monitoring of clinically relevant,CTC-based biomarkers that can be analyzed routinely without invasive *** molecular platforms have been used to investigate the molecular profile of the disease,from high throughput gene expression analyses down to single cell biological *** established presence of CTC heterogeneity nevertheless constitutes a challenge for cell isolation as the several subpopulations can potentially display different molecular characteristics;in this scenario,careful consideration must be given to the isolation approach,whereas methods that discriminate against certain subpopulations may result in the exclusion of CTCs that carry biological *** the context of prostate cancer,CTC molecular interrogation can enable longitudinal monitoring of key biological features during treatment with substantial clinical impact,as several biomarkers could predict tumor response to AR signaling inhibitors(abiraterone,enzalutamide)or standard chemotherapy(taxanes).Thus,CTCs represent a valuable opportunity to personalize medicine in current clinical practice.

关键词： Circulating tumor cells liquid biopsy prostate cancer precision medicine predictive biomarkers targeted therapy

Towards predicting biochar impacts on plant-available soil nitrogen content

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Biochar 2022年第1期4卷 1040-1054页

作者： Claire L.Phillips Kylie M.meyer Manuel Garcia-Jaramillo Clara S.Weidman Catherine E.Stewart Thomas Wanzek Michael A.Grusak Donald W.Watts Jeff Novak Kristin M.Trippe USDA-ARS National Laboratory for Agriculture and Environment AmesIAUSA USDA-ARS Forage Seed and Cereal Research Unit CorvallisORUSA Department of Environmental Toxicology Oregon State UniversityCorvallisORUSA Department of Crop and Soil Science Oregon State UniversityCorvallisORUSA USDA-ARS Soil Management and Sugarbeet Research Unit Ft.CollinsCOUSA USDA-ARS edward T.Schafer Agricultural Research center FargoNDUSA USDA-ARS Coastal Plain Soil Waterand Plant Research CenterFlorenceSCUSA

Biochars can improve soil health but have been widely shown to reduce plant-available nitrogen(N)owing to their high carbon(C)content,which stimulates microbial ***,because biochars contain large amounts of C that are not microbially available,their total elemental C:N ratio does not correspond well with impacts on soil *** hypothesized that impacts on soil plant-available N would relate to biochar mineralizable-C(C_(min))content,and that C:N ratios of the mineralizable biochar component could provide a means for predicting conditions of net soil N-mineralization *** conducted two laboratory experiments,the first measuring biochar C_(min)from respiration of isotopically labeled barley biochars manufactured at 300,500,and 750℃,and the second characterizing C_(min)by proxy measurements for ten biochars from six feedstocks at several *** both experiments,soils were incubated with 2%biochar by mass to determine impacts to soil *** to expectation,all the biochars increased soil N-mineralization relative to unamended *** unexpected,higher temperature(500 and 700℃)barley biochars with less C_(min)stimulated more soil decomposition and more soil N-mineralization than a 350℃barley ***,across diverse biochar feedstocks and production methods,none of the biochar characteristics correlated with soil *** finding of improved soil N-mineralization adds complexity to the range of soil N responses that can be expected in response to biochar *** of the limited ability to predict soil N responses from biochar properties,users should monitor soil N to manage soil fertility.

关键词： C:N ratio Plant-available nitrogen Priming Respiration ^(13)C

Gene variants of the phosphatidylcholine synthesis pathway do not contribute to RDS in the Chinese population

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World Journal of Pediatrics 2018年第1期14卷 52-56页

作者： Yu-Jun Chen Julia meyer Jennifer A.Wambach Kelcey DePass Daniel J.Wegner Xin Fan Qun-Yuan Zhang Heins Hillary F.Sessions Cole Aaron Hamvas Neonatology the First Affliated Hospital of GuangxiMedical UniversityNanningChina Division of Newborn Medicine Edward MallinckrodtDepartment of PediatricsWashington University Schoolof MedicineSt.LouisUSA

Background To determine population-based prevalence and disease contribution of phosphatidylcholine synthetic pathway-associated gene variants in a native southern Chinese cohort. Methods We used bloodspots from 2010 that were obtained from the Guangxi Neonatal Screening center in Nannning China and included the Han (n = 443) and Zhuang (n = 313) ethnic groups. We sequenced the exons of cholinephosphate cytidylyltransferase (PCYT1B) lysophospholipid acyltransferase 1 (LPCAT1), and cholinephosphotransferase (CHPT1) genes, and analyzed both rare and common exonic variants. Results We obtained five mutations (G199D, A299V, G434C, Y490C, L312S) with eight alleles in the three candidate genes. The collapsed minor allele frequency for candidate genes was not significantly different between the Han and Zhuang popula-tions (0.0045 vs. 0.0064, respectively,P = 0.725). The combined Han and Zhuang pool collapsed carrier frequency of rare mutation allele was found to be 1.06%, which is much higher than previously reported for the Missouri population (0.1%). Further, we detected six exonic common variants (three in LPCAT1 and three in CHPT1), with three non-synonymous vari-ants (F162S, F341L, M427K) among them. Two of the non-synonymous exonic variants (F341L, M427K) were not found in CHB;F341L was also not previously reported in exome sequencing project. Conclusions The population-based frequency of mutations in the phosphatidylcholine synthesis pathway-associated genes PCYT1B LPCAT1,CHPT1 is low in southern Chinese newborns and there is no evidence of contribution to population-based disease burden of respiratory distress syndrome. As a population-based study of rare mutations and common variants, this work is valuable in directing future research.

关键词： Genetic epidemiology Human population genetics Neonatal respiratory distress syndrome Pulmonary surfactant

Transcranial magnetic stimulation: potential treatment for co-occurring alcohol, traumatic brain injury and posttraumatic stress disorders

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Neural Regeneration Research 2014年第19期9卷 1712-1730页

作者： Amy A.Herrold sandra L.Kletzel Brett C.Harton R.Andrew Chambers Neil Jordan Theresa Louise-Bender Pape edward Hines Jr.VA Hospital Research Service PO Box 5000 (M/C 151H)HinesILUSA The Department of Veterans Affairs (VA) Center for Innovation for Complex Chronic HealthcareEdward Hines Jr.VA HospitalPO Box 5000 (M/C 151H)HinesILUSA Department of Psychiatry & Behavioral Sciences Northwestern University Feinberg School of Medicine446 East Ontario#7-200ChicagoILUSA Chicago Association for Research and Education in Science HinesILUSA Department of Psychiatry Laboratory for Translational Neuroscience of Dual Diagnosis & DevelopmentNeuroscience Research CenterIndiana University School of Medicine320 West 15~(th)StreetIndianapolisINUSA Northwestern University Feinberg School of Medicine Department of Physical Medicine and RehabilitationOffice of Medical Educ.(1574)345 E.Superior St.ChicagoILUSA

Alcohol use disorder （AUD）, mild traumatic brain injury （mTBI）, and posttraumatic stress disorder （PTSD） commonly co-occur （AUD ＋ mTBI ＋ PTSD）. These conditions have overlapping symptoms which are, in part, reflective of overlapping neuropathology. These conditions become problematic because their co-occurrence can exacerbate symptoms. Therefore, treatments must be developed that are inclusive to all three conditions. Repetitive transcranial magnetic stimulation （rTMS） is non-invasive and may be an ideal treatment for co-occurring AUD ＋ mTBI ＋ PTSD. There is accumulating evidence on rTMS as a treatment for people with AUD, mTBI, and PTSD each alone. However, there are no published studies to date on rTMS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. This review article advances the knowledge base for rTMS as a treatment for AUD ＋ mTBI ＋ PTSD. This review provides background information about these co-occurring conditions as well as rTMS. The existing literature on rTMS as a treatment for people with AUD, TBI, and PTSD each alone is reviewed. Finally, neurobiological findings in support of a theoretical model are discussed to inform TMS as a treatment for co-occurring AUD ＋ mTBI ＋ PTSD. The peer-reviewed literature was identified by targeted literature searches using PubMed and supplemented by cross-referencing the bibliographies of relevant review articles. The existing evidence on rTMS as a treatment for these conditions in isolation, coupled with the overlapping neuropathology and symptomology of these conditions, suggests that rTMS may be well suited for the treatment of these conditions together.

关键词： transcranial magnetic stimulation traumatic brain injury posttraumatic stress disorder treatment neuroimaging substance use disorders addiction co-morbidity mental health disorders behavioral health neuroimaging non-invasive brain stimulation

A Biological Restoration Model for Contaminated Coastal Marshes and Islands Using the Life Cycle of Acheta domesticus to Establish Environmental Sustainability

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Computational Water, Energy, and Environmental Engineering 2020年第2期9卷 13-21页

作者： Anna Leyrer edward Bush James Geaghan Buffy meyer St. Joseph’s Academy Baton Rouge Louisiana USA Ag center Louisiana State University Baton Rouge LA USA Emeritus Department of Experimental Statistics Louisiana State University Baton Rouge LA USA Louisiana Department of Agriculture and Forestry Baton Rouge LA USA

Insects such as Acheta domesticus account for over half of marsh fish and migratory bird diet. Therefore, insects are very important to marsh and island ecosy stems and are susceptible to oil contamination, but little research has been done to study the effects of oil spills on cricket populations. The purpose of this experiment was to determine the effects of an oil spill event on Acheta domesticus mortality and hatch rate to establish environmental sustainability. The treatment groups included 0% oil contamination, 5% oil contamination and 10% oil contamination. The scientist counted the number of deaths in two-week, four-week, and six-week-old crickets after oil contamination. In addition, the scientist counted the number of hatchlings among treated cricket eggs. Error bar lines in the results section supported the scientist’s hypothesis that the crickets would be affected by oil contamination. In fact, over 90% of the 10% oil treatment group died and over 80% of the 5% oil treatment group died after five days of oil contamination in the six-week-old experiment. The scientist used a Gas Chromatography Mass Spectrometer to determine if benzene, toluene, ethylbenzene, or xylene (total) were present in the sediment samples. BTEX exposure is suspected to possibly cause insect mortality. These volatile organic compounds were present in the samples and were found in higher quantities in samples with higher concentrations of oil. The highest quantity of volatile organic compounds present was xylene. After studying the population dynamics of the tested Acheta domesticus, the scientist found that the two-week and four-week-old crickets’ survivability could fit a linear model while the six-week-old crickets fit an exponential model. The scientist used these models to observe how long it took each treatment group to approach zero, and the oiled groups grew closer to a population of zero significantly faster. For example, it took about twenty-seven days for the 10% treatment

关键词： Entomology Contamination Oil Insects Sustainability Marsh

Deciphering the Role of Klf10 in the Cerebellum

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Journal of Biomedical Science and Engineering 2022年第5期15卷 140-156页

作者： Malek Kammoun Lydie Nadal-Desbarats sandra Même Aude Lafoux Corinne Huchet Géraldine meyer-Dilhet Julien Courchet Frédéric Montigny Frédéric Szeremeta William Même Vladimir Veksler Jérôme Piquereau Philippe Pouletaut Malayannan Subramaniam John R. Hawse Jean-Marc Constans Sabine F. Bensamoun Biomechanics and Bioengineering CNRS UMR 7338 Sorbonne University—University of Technology of Compiègne Compiègne France iBrain CNRS UMR 1253 University of Tours Tours France center for Molecular Biophysics CNRS UPR4301 Orléans France Therassay Platform University of Nantes Nantes France INSERM UMR1089 University of Nantes Nantes France CNRS UMR-5310 and INSERM U-1217 NeuroMyoGène Institute Villeurbanne France INSERM PST-ASB University of Tours Tours France INSERM UMR-S 1180 University of Paris-Saclay Chatenay-Malabry France Department of Biochemistry and Molecular Biology Mayo Clinic Rochester USA CHIMERE EA7516 UPJV Faire Faces Institute Amiens France

Recent studies have demonstrated a new role for Klf10, a Krüppel-like transcription factor, in skeletal muscle, specifically relating to mitochondrial function. Thus, it was of interest to analyze additional tissues that are highly reliant on optimal mitochondrial function such as the cerebellum and to decipher the role of Klf10 in the functional and structural properties of this brain region. In vivo (magnetic resonance imaging and localized spectroscopy, behavior analysis) and in vitro (histology, spectroscopy analysis, enzymatic activity) techniques were applied to comprehensively assess the cerebellum of wild type (WT) and Klf10 knockout (KO) mice. Histology analysis and assessment of locomotion revealed no significant difference in Klf10 KO mice. Diffusion and texture results obtained using MRI revealed structural changes in KO mice characterized as defects in the organization of axons. These modifications may be explained by differences in the levels of specific metabolites (myo-inositol, lactate) within the KO cerebellum. Loss of Klf10 expression also led to changes in mitochondrial activity as reflected by a significant increase in the activity of citrate synthase, complexes I and IV. In summary, this study has provided evidence that Klf10 plays an important role in energy production and mitochondrial function in the cerebellum.

关键词： Klf10 Cerebellum Mice Magnetic Resonance Imaging and Spectroscopy Metabolomics Mitochondria