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Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

Journal of Cancer Therapy 2024年第4期15卷 99-120页

作者： Sheba Goklany John C. Oertle III Ronald Matthias Jr. Daniel Warren David Medina Rory Sears Robert Zieve Kendra Quart Christopher Aussems Jon Moma Shannon Miller Zach Poteet Conner Coffin courtney middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin Daniel Conway Chad Burk Ruth Tan-Lim Dino Prato Envita Medical Centers Scottsdale AZ USA

New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

关键词： Envita Medical Centers Late-stage Cancer Overall Response Rate Quality of Life Circulating Tumor Cells (CTCs) Mutant Allele Frequency (MAF) Precision Care

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Mucopolysaccharidosis typeⅢB:a current review and exploration of the AAV therapy landscape

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Neural Regeneration Research 2024年第2期19卷 355-359页

作者： courtney J.Rouse Victoria N.Jensen Coy D.Heldermon Lacerta Therapeutics AlachuaFLUSA University of Florida College of Medicine GainesvilleFLUSA

Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for *** results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological *** treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢ***-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential *** group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy ***,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.

关键词： adeno-associated virus central nervous system gene therapy heparan sulfate immune response mucopolysaccharidoses type IIIB N-acetyl-alpha-glucosaminidase newborn screening

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The use of Montgomery salivary bypass tubes and pharyngocutaneous fistula following salvage laryngectomy

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 43-48页

作者： courtney B.Shires Mackenzie Latour Merry Sebelik Karuna Dewan West Cancer Center GermantownTennesseeUSA Department of Otolaryngology-Head and Neck Surgery Louisiana State University Health ShreveportShreveportLouisianaUSA Department of Otolaryngology-Head and Neck Surgery Emory UniversityAtlantaGeorgiaUSA

Objectives:Pharyngocutaneous fistula(PCF)is the most common complication to follow total laryngectomy(TL)and is associated with increases in length of hospital stay and with a need for revision surgery or readmission,as well as with delays in return to oral *** who require salvageTL(STL)or primary(chemo)radiation therapy are at higher risk for developing *** to the quality‐of‐life burden of PCF on patients,limiting this occurrence is ***:We conducted a retrospective cohort study of patients undergoing STL with placement of Montgomery salivary bypass tube(MSBT)^(TM)for at least 2 weeks duration between 2013 and 2017 at a single *** patients all underwent free flap *** primary outcome of interest was development of *** outcomes included demographics,previous treatment,base of tongue(BOT)involvement,extent of defect,concurrent neck dissection(ND),and margin ***χ^(2) analysis was used to evaluate factors associated with ***:Forty‐four patients underwent STL with Montgomery tube placement and free flap *** developed PCF(18.2%).The average age was 61.6 years;36 patients were male(81.8%),whereas eight patients were female(18.2%).There was no association between PCF and previous chemoradiation versus radiation(15.8%vs.33.3%,P<0.30),BOT involvement versus not(11.1 vs.22.2%,P<0.38),circumferential versus partial defect(18.8%vs.17.9%,P<0.94),ND versus none(10%vs.25%,P<0.20),or margin ***:PCF complicated 18.2%of STL cases at our institution and was not associated with differences in primary treatment modality,presence of concomitant ND,extent of pharyngeal defect,BOT involvement,or positive frozen or permanent surgical margin.

关键词： free flap reconstruction Montgomery pharyngocutaneous fistula salivary bypass tube salvage total laryngectomy total laryngectomy

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Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

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Journal of Cancer Therapy（癌症治疗） 2024年第4期 99页

作者： Sheba Goklany John C.Oertle III Ronald Matthias Jr. Daniel Warren David Medina Rory Sears Robert Zieve Kendra Quart Christopher Aussems Jon Moma Shannon Miller Zach Poteet Conner Coffin courtney middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin Daniel Conway Chad Burk Ruth Tan-Lim Dino Prato

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秸秆-磷石膏联用对赤泥的腐殖质组分和微生物群落的影响

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Journal of Central South University 2024年第2期31卷 460-476页

作者：吴昊朱轩郅唐崇俭黄诗蔚孙伟江钧朱锋杨兴旺 RONAN courtney 薛生国 School of Metallurgy and Environment Central South UniversityChangsha 410083China School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China Department of Life Sciences Schrodinger BuildingUniversity of LimerickLimerick V94 T9PXIreland

腐殖化过程是赤泥土壤化及堆场生态修复的重要环节。本研究采用腐殖质分级和高通量测序技术,探究了秸秆和磷石膏联用对赤泥腐殖质组分和微生物群落的影响。结果表明,秸秆-磷石膏联用显著增加赤泥胡敏酸和富里酸含量,提高微生物群落多样... 详细信息

腐殖化过程是赤泥土壤化及堆场生态修复的重要环节。本研究采用腐殖质分级和高通量测序技术,探究了秸秆和磷石膏联用对赤泥腐殖质组分和微生物群落的影响。结果表明,秸秆-磷石膏联用显著增加赤泥胡敏酸和富里酸含量,提高微生物群落多样性和丰富度,促进赤泥腐殖化过程。施用秸秆后,赤泥中葡萄糖苷酶、纤维素水解酶、多酚氧化酶和过氧化物酶分别升高7.15~8.76倍、5.64~7.12倍、2.69~4.57倍和2.59~4.24倍,显著增加Devosiaceae、Rhizobiaceae、Flavobacteriaceae、Caulobacteraceae和Cellvibrionaceae等具有纤维素降解和固氮功能微生物类群相对丰度,提高微生物群落稳定性。研究结果为外源生物质促进腐殖质累积、驱动赤泥成土进程提供科学依据。

关键词：赤泥秸秆腐殖质组分微生物群落赤泥土壤化

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Spontaneous Tumor Lysis Syndrome Secondary to Iatrogenic Acute Kidney Injury: A Case Report

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Case Reports in Clinical Medicine 2024年第5期13卷 155-161页

作者： Joseph Capito Mitchell Hoyson Amie M. Ashcraft Hassan Suleiman courtney S. Pilkerton Department of Family Medicine West Virginia University Morgantown WV USA Department of Clinical Family Medicine University of Rochester Medical Center Rochester NY USA Departments of Critical Care Medicine & Nephrology Mount Sinai New York City NY USA

Spontaneous Tumor Lysis Syndrome (STLS) is a rare oncologic condition caused by the breakdown of neoplastic tissue in the absence of traditional anti-tumor therapy. It is postulated that cancers with rapidly dividing cells lead to increased cell turnover which exceeds the kidneys’ ability to adequately filtrate by-products of cellular breakdown (i.e., phosphate, potassium, anduric acid), leading to end organ damage. It has been reported in the past that kidney failure is a sequelae of Tumor Lysis Syndrome (TLS), but there have been no reports that demonstrate acute kidney injury (AKI) preceding TLS. The case presented here demonstrates TLS in a patient with no formal cancer diagnosis, who had received no chemotherapy or radiation that was precipitated by an iatrogenic AKI with chlorthalidone and ibuprofen. This unusual pattern of AKI preceding STLS may provide insight into the pathophysiology of the condition and could possibly lead to greater understanding of this phenomenon.

关键词： Spontaneous Tumor Lysis Acute Kidney Injury Lymphoma Chlorthalidone NSAID

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An Automated,Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

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Precision Chemistry 2024年第2期2卷 57-62页

作者： Ann Adele Byars Khushi R.Kompally Emily Mechnick Reilly E.Sonstrom Alexander Mikhonin Justin L.Neill Ruth Boetzel James MacGregor courtney Talicska Jian Li Yizhou Liu BrightSpec Inc.CharlottesvilleVirginia 22903United States Pfizer R&D UK Limited Sandwich CT139NJUnited Kingdom Analytical Research and Development Pfizer Research and DevelopmentGrotonConnecticut 06340United States

Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these *** this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring *** interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and *** reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol *** spectrometer was able to provide kinetic information about the reaction and determine reaction *** the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.

关键词： molecular rotational resonance spectroscopy reaction monitoring reaction kinetics isotopes process analytical technology

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Tomato fruit as a model for tissue-specific gene silencing in crop plants

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Horticulture Research 2020年第1期7卷 839-845页

作者： Ari Feder Sarah Jensen Anquan Wang Lance courtney Lesley middleton Joyce Van Eck Yongsheng Liu James J.Giovannoni Boyce Thompson Institute for Plant Research Cornell UniversityIthacaNYUSA Section of Plant Breeding and Genetics Cornell UniversityIthacaNYUSA School of Biotechnology and Food Engineering Hefei University of Technology230009 HefeiChina Section of Plant Biology Cornell UniversityIthacaNYUSA US Department of Agriculture–Agricultural Research Service Robert W.Holley Center for Agriculture and HealthIthacaNYUSA

Use of CRISPR-Cas9(Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-CRISPR-associated 9)-mediated genome editing has proliferated for use in numerous plant species to modify gene function and expression,usually in the context of either transient or stably inherited genetic *** extremely useful in many applications,modification of some loci yields outcomes detrimental to further experimental evaluation or viability of the target *** of Cas9 under a promoter conferring gene knockouts in a tissue-specific subset of genomes has been demonstrated in insect and animal models,and recently in *** developed an in planta GFP(green fluorescent protein)assay system to demonstrate fruit-specific gene editing in tomato using a phosphoenolpyruvate carboxylase 2 gene *** then targeted a SET-domain containing polycomb protein,SlEZ2,previously shown to yield pleiotropic phenotypes when targeted via ^(35)S-driven RNA interference and we were able to characterize fruit phenotypes absent additional developmental ***-specific gene editing will have applications in assessing function of essential genes otherwise difficult to study via germline modifications and will provide routes to edited genomes in tissues that could not otherwise be recovered when their germline modification perturbs their normal development.

关键词： otherwise specific editing

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Histone Deacetylase Genes in Arabidopsis Development

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Journal of Integrative Plant Biology 2008年第7期50卷 875-885页

作者： courtney Hollende Department of Cell Biology and Molecular Genetics University of Maryland College ParkMaryland 20742USA

Histone acetylation and deacetylation are directly connected with transcriptional activation and silencing in eukaryotes. Gene families for enzymes that accomplish these histone modifications show surprising complexity in domain organization, tissue-specific expression, and function. This review is focused on the family of histone deacetylases （HDACs） that remove the acetyl group from core histone tails, resulting in a ＂closed＂ chromatin and transcriptional repression. In Arabidopsis, 18 HDAC genes are divided into three different types - RPD3-1ike, HD-tuin and sirtuin - with two or more members in each type. The structural feature of each HDAC class, the expression profile of each HDAC gene during development and functional insights of important family members are summarized here. It is clear that HDACs are an important class of global transcriptional regulators that play crucial roles in plant development, defense, and adaptation.

关键词： chromatin epigenetic regulation gene silencing histone deacetylase plant development

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Role of MGST1 in reactive intermediate-induced injury

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World Journal of Gastroenterology 2011年第20期17卷 2552-2557页

作者： courtney S Schaffert Department of Biochemistry and Molecular Biology University of Nebraska Medical Center

Microsomal glutathione transferase (MGST1, EC 2.***.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.

关键词： Microsomal glutathione transferase 1 Oxidative stress Mitochondrial permeability transition Glutathione Liver injury

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