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Journal articles on the topic 'Regular Baptists'
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Fox, Aaron A., and Jeff Titon. "Songs of the Old Regular Baptists." Yearbook for Traditional Music 30 (1998): 189. http://dx.doi.org/10.2307/768590.
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Robie, Harry. "The Old Regular Baptists of Central Appalachia." Appalachian Heritage 19, no. 1 (1991): 67–68. http://dx.doi.org/10.1353/aph.1991.0102.
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Harper, Keith. "“And All the Baptists in Kentucky Took the Name United Baptists”: The Union of the Separate and Regular Baptists of Kentucky." Register of the Kentucky Historical Society 110, no. 1 (2012): 3–31. http://dx.doi.org/10.1353/khs.2012.0001.
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Guth, James, and Howard Dorgan. "The Old Regular Baptists of Central Appalachia: Brothers and Sisters in Hope." Journal for the Scientific Study of Religion 30, no. 2 (June 1991): 217. http://dx.doi.org/10.2307/1387219.
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Drake, Richard B., and Howard Dorgan. "The Old Regular Baptists of Central Appalachia: Brothers and Sisters in Hope." Journal of Southern History 57, no. 3 (August 1991): 545. http://dx.doi.org/10.2307/2209985.
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Leonard, Bill J. "Book Review: The Old Regular Baptists of Central Appalachia Brothers and Sisters in Hope." Review & Expositor 88, no. 4 (December 1991): 476. http://dx.doi.org/10.1177/003463739108800439.
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Smith, Larry Douglas. "The Old Regular Baptists of Central Appalachia: Brothers and Sisters in Hope. By Howard Dorgan. Knoxville: The University of Tennessee Press, 1989. xxiii + 269 pp. $27.50." Church History 61, no. 2 (June 1992): 273–74. http://dx.doi.org/10.2307/3168296.
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Harper, Keith. "Order and Ardor: The Revival Spirituality of Oliver Hart & the Regular Baptists in Eighteenth-Century South Carolina. By Eric C. Smith. Foreword by Thomas S. Kidd. The University of South Carolina Press, 2018. xv + 145 pp. $44.99 hardcover; $44.99 ebook." Church History 88, no. 3 (September 2019): 855–57. http://dx.doi.org/10.1017/s0009640719002269.
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Dorgan, Howard. ""Ol Time Way" Exhortation: Preaching in the Old Regular Baptist Church." Journal of Communication and Religion 10, no. 2 (1987): 24–30. http://dx.doi.org/10.5840/jcr198710210.
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Y.A., Adewale, Adelakun E.A., Atowoju A.A., and Adelakun A.O. "Implication of Religious Syncretism on Baptist Mission Work in Ojo Island, Lagos State Nigeria." African Journal of Culture, History, Religion and Traditions 6, no. 2 (December 28, 2023): 86–97. http://dx.doi.org/10.52589/ajchrt-qacfwflh.
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Baptist is one of the denominations and mission agencies that have been doing mission work in Ojo Island for several decades now. However, the mission work in Ojo Island is not without challenges such as poverty, cultural affiliation and idolatry, but this study focuses on religious syncretism. Therefore, the study investigated factors responsible for religious syncretism in Ojo Island, Lagos State, Nigeria with a view to identify ways of strengthening the Baptist mission work. The framework for the study was premised on theology of mission, which underscores that mission found its basis in God’s love and redemptive plan through Jesus. Descriptive survey design was adopted while questionnaires were administered to two hundred and twenty-three (223) members of the selected Baptist churches using the purposive random sampling method. The data generated was analysed through frequency count, bar chart and pie chart. Factors responsible for religious syncretism on the Baptist mission in Ojo Island include: assumption that all religious traditions are relative and complimentary, community background and economic life, seeking for rescue in a time of crisis and insecurity, family ties and brotherhood relationship. All these constitute a serious challenge and setback for the Baptist mission efforts in Ojo Island. The study recommends contextual biblical preaching, discipleship, power evangelism, and social actions such as regular medical mission and vocational training as means of strengthen the Baptist mission work in Ojo Island.
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Hyrina, T. "СТАНОВЛЕННЯ ПРОФЕСІЙНОЇ КОМПЕТЕНТНОСТІ ПРОДУЦЕНТІВ РАДІОПРОГРАМ ДУХОВНОЇ ТЕМАТИКИ В УКРАЇНСЬКІЙ ЕМІГРАЦІЇ." State and Regions. Series: Social Communications, no. 1(49) (March 23, 2022): 42. http://dx.doi.org/10.32840/cpu2219-8741/2022.1(49).6.
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<p><strong><em>The purpose</em></strong><em> of the article is to comprehend the aspect of religious radio broadcasting in the structure of radio programs of Ukrainian emigration in the radio space of foreign countries in the twentieth century.</em></p><p><strong><em>The research methodology </em></strong><em>is based on the use of general scientific methods of archival research (digitized issues of the Ukrainian daily «Svoboda» in 1935–1991 available in free access), monitoring of identified mentions of the presence of Ukrainian-language programs in the radio space of different countries, clipping , the names of the program, its periodicity, the name of the radio station on which the broadcasts were available, the areas covered by it, characteristics, references to the source of information and its author, etc., historiographical, systematization, deductive and method of observation.</em></p><p><strong><em>Results.</em></strong><em> </em><em>As a result of the research, the orientation of Ukrainians to spiritual practices and religious themes in the radio space of foreign countries was stated. The founders of the programs for Ukrainian believers were representatives of various religious organizations in North and South America, Europe and even Australia. Based on the capabilities of the organizers, the programs were created on a regular basis, and broadcast on a permanent broadcast network, as well as non-periodic holidays and annual anniversaries. Priests and members of their families became the authors and hosts of such programs. The team of radio amateurs included a treasurer who was responsible for collecting and rationally using funds donated by the community and provided by the flock to support the presence of the Ukrainian word of God in the radio space. Some programs, such as Evangelical Morning, a project of Ukrainian Baptists in North America, were briefly spread to Soviet Ukraine, from where they received grateful feedback from underground listeners. The main religious holidays were timed to broadcast the Divine Liturgy, for the sick, those who do not have the opportunity to join the action in person</em></p><p><strong><em>Novelty.</em></strong><em> For the first time in the scientific discourse the achievements of the spiritual and religious segment of the radio programs of the Ukrainian emigration in the XX century are comprehended.</em></p><p><strong><em>The practical significance</em></strong><em> of the research results is the introduction of documented data on the state of development, achievements and thematic, genre diversity, musical diversity and polyphony of Ukrainian radio programs on the spiritual life of Ukrainians in different countries.</em></p><p><strong><em>Key words:</em></strong><em> Ukrainian-language radio program, Radio Service of God, radio broadcast, religious radio program, world Ukrainian radio.</em></p>
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Vaculík, Jaroslav. "The Czech School Foundation in Volhynia, 1921–1939." Czech-polish historical and pedagogical journal 13, no. 1 (June 3, 2022): 3–12. http://dx.doi.org/10.5817/cphpj-2021-001.
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It was certainly a great merit of the Czech School Foundation (CSF) that it undertook the difficult task of organizing Czech private education in Volhynia in accordance with the provisions of the Czechoslovak-Polish Treaty. The most difficult thing was to overcome the lack of funds, which were being obtained in the form of regular fund-raising collections once or twice a year and extraordinary fund-raising events on various occasions – parties, weddings, baptisms, etc. The Czech education system in Volhynia also received material assistance (textbooks, pupils’ libraries, teachers) from the school administration of the Czechoslovak Republic and from Comenius, the Association for the Support of Czechoslovak Foreign Schools.
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Hankins, Barry. "One in Hope and Doctrine: Origins of Baptist Fundamentalism, 1870–1950. By Kevin Bauder and Robert Delnay. Schaumburg, Ill.: Regular Baptist Books, 2014. 396 pp. $29.99 paper." Church History 85, no. 2 (May 27, 2016): 412–14. http://dx.doi.org/10.1017/s0009640716000287.
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Patterson, Sarah. "Understanding Christianity Through Presentation and Practice." OKH Journal: Anthropological Ethnography and Analysis Through the Eyes of Christian Faith 7, no. 2 (July 31, 2023): 28–38. http://dx.doi.org/10.18251/okh.v7i2.185.
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Having grown up in the Midwest, I have seen the localized practice of Christianity as a way of life for many members of small communities. Christian protocols cultivate a mindset of fellowship outside the sanctuary. Praying for members of the community that do and do not regularly attend services instilled in me a curiosity about community dynamics through religious practices. This research-based study describes the congregation of a small country church known as The Harmony Church through regular attendance at Sunday services, weekly music practices, Bible study, and prayer meetings as well as monthly business meetings. Using ethnographic methods of participant observation and interviews, I discuss how the congregation understands and values their General Baptist Christian practice locally, as well as perceive its presentation globally.
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Stanley, Brian. "‘The Miser of Headingley’: Robert Arthington and the Baptist Missionary Society, 1877–1900." Studies in Church History 24 (1987): 371–82. http://dx.doi.org/10.1017/s0424208400008457.
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A gravestone in a Teignmouth cemetery displays the following inscription: Robert ArthingtonBorn at Leeds May 20th, 1823Died at Teignmouth Oct. 9th, 1900His life and his wealth were devoted to the spread of the Gospel among the Heathen.That unassuming epitaph bears testimony to one of the most remarkable figures in the story of Victorian missionary expansion. The missionary movement from both Britain and North America depended for its regular income on the enthusiasm of the small-scale contributor, but the munificence of the wealthy was essential to the financing of special projects or the opening up of new fields. The role of, for example, the jam manufacturer William Hartley as treasurer of the Primitive Methodist Missionary Society, or of the chemical manufacturers James and John Campbell White in providing much of the finance for the Free Church of Scotland’s Livingstonia Mission, is relatively well known.
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Zapadenko, Igor. "REGULAR GARDEN OF THE 18TH CENTURY AT MEDZHYBIZH CASTLE IN DOCUMENTS AND CARTOGRAPHY." Current Issues in Research, Conservation and Restoration of Historic Fortifications 2023, no. 19 (2023): 54–70. http://dx.doi.org/10.23939/fortifications2023.19.054.
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There is a widespread opinion in local history and some scientific publications that in the 18th century, especially in the ownership of the Czartoryski princes, Medzhybizh castle was transformed into a luxury romantic residence. The decorative garden was allegedly created as a result of Izabella Czartoryskas interest in English parks, as a continuation of the architectural program of the main residence in Pulawy. There is even a statement that the garden was arranged in the inner territory of Medzhybizh castle. Nonetheless, the inventories of the Medzhybizh estate indicate that during the 18th century, Medzhybizh castle was utilized not for residential purposes, but also for economic and occasionally military purposes. The notion of a grandiose ornamental garden at the Medzhybizh castle is merely an adaptation of the romantic descriptions of the real romantic park at the Czartoryski main residence called Pulawy (in Poland). Only the Polish researcher Rafal Nestorow has provided real information about the existence of the Medzhybizh garden, which was called the Italian garden. TThis garden was established by Jan Baptista Dessieur in the year 1713. Nestorows research is based on archival documents obtained from the library of Princes Czartoryski in Kraków (Poland). Nonetheless, in his perspective, the precise location of this “Italian garden” remains ambiguous. This article extends and clarifies the research initiated by R. Nestorow. The archival inventories from the 1750s provide a thorough description of the "Italian garden" near the Medzhybizh castle, which was not located in the town of Medzhybizh, but in a nearby suburb called Stawnica. The article explains the location, description of buildings, and list of plants in the so-called “Italian garden”, which belonged to the owners of the Medzhybizh in the 18th century. The differences between this garden and the classic Italian landscape are also explained. The location of the Italian garden surrounding the castle and the streets of the modern Stawnica is revealed by archival maps of Medzhybizh from the 18th and 19th centuries. The article explains where the Italian garden is, what houses it has, and what plants it has. The garden was owned by the Medzhybizh family in the 18th century. The elucidation of the distinctions between this garden and the traditional Italian landscape is also provided.
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Fuentes Peralta, Mario, and Carolina Chávez Preisler. "Abandono escolar: circunstancias que caracterizan el momento del abandono escolar temprano." Revista INTEREDU 1, no. 1 (January 27, 2021): 74–93. http://dx.doi.org/10.32735/s2735-65232019000181.
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El tema que se desarrolla en el presente artículo aborda los factores asociados a la deserción escolar. Entenderemos como equivalentes los conceptos de abandono y deserción. La deserción es comprendida como el abandono temporal o definitivo del sistema educativo por parte de un estudiante de educación obligatoria (Centro de Estudios de opinión Ciudadana [CEOC], 2009). El objetivo del artículo consiste en caracterizar las circunstancias que rodean la deserción escolar en aquellos estudiantes que abandonaron la educación diurna, y decidieron continuar con sus estudios en Educación de Jóvenes y Adultos (EDJA) del Colegio Emprender Osorno. La metodología utilizada para esta investigación es cuantitativa (Hernández, Fernández y Baptista, 2003), y la muestra fue conformada por 85 estudiantes que habían abandonado el sistema de educación regular diurna, y que al momento de realizar esta investigación ya se encontraban inscritos en el programa de educación para jóvenes y adultos, en jornada vespertina. El instrumento de recogida de información que se utilizó fue un cuestionario con preguntas cerradas. Los resultados permitieron reconocer que las circunstancias que rodean al momento del abandono escolar son multifactoriales y que suelen tener relación con la familia, el establecimiento y el contexto socioeconómico.
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Chavarro-Bermúdez, Lizet Johana, Carlos Capella-Peris, Oscar Chiva-Bartoll, and Marc Pallarés-Piquer. "Promoción de la educación inclusiva e intercultural: estudio de caso en un colegio rural colombiano." Revista Lasallista de Investigación 17, no. 2 (March 31, 2021): 256–65. http://dx.doi.org/10.22507/rli.v17n2a18.
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Introducción: debido al fenómeno de globalización actual, cada vez es más necesario aportar una visión inclusiva e intercultural al ámbito educativo. No responder adecuadamente a esta demanda puede provocar situaciones de exclusión, segregación y discriminación del alumnado. El gobierno colombiano ha planteado diferentes acciones para fortalecer este enfoque y evitar dichas problemáticas. No obstante, estas acciones deben ser analizadas en profundidad para evidenciar la promoción de la educación inclusiva e intercultural en las instituciones educativas. Objetivo: el propósito de la investigación es determinar el nivel de conocimiento y ejecución de las prácticas inclusivas e interculturales en el Colegio Llano de Palmas (Colombia). Materiales y métodos: el diseño de investigación se acomete mediante un estudio de caso. La metodología utilizada es cuantitativa descriptiva (Hernández, Fernández & Baptista, 2010), implementando el cuestionario sobre el reconocimiento y aplicabilidad de la competencia inclusiva e intercultural. Resultados: el análisis de datos revela que la educación inclusiva e intercultural apenas se fomenta de forma regular en el centro educativo (10 %), siendo mayoritaria su promoción inadecuada (90 %) mediante una implementación esporádica (49 %), no aplicándose en absoluto (36 %) o desconociendo por completo su estado de desarrollo (5 %). Conclusiones: los resultados obtenidos indican que el conocimiento y la ejecución de prácticas inclusivas e interculturales en el Colegio Llano de Palmas es notablemente mejorable. Esta situación demanda el diseño y aplicación de estrategias específicas de promoción más efectivas, así como el análisis de distintos entornos educativos para determinar la situación actual del país en este sentido.
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Buzykina, Yulia. "Aesthetic judgments of Vasily Grigorovich-Barsky on the example of descriptions of architecture." St. Tikhons' University Review. Series V. Christian Art 46 (June 30, 2022): 59–73. http://dx.doi.org/10.15382/sturv202246.59-73.
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Describing his wanderings in famous travelogue, Vassiliy Grigorovich-Barskiy was paying special attention to architecture. As time went on, the descriptions became more specific, which makes it possible to articulate his aesthetic views. In the beginning of his wanderings, he just says that Italian architecture of palaces and churches is beautiful. Then, in Venice, he describes with piety the cathedral of St Marco, which was, to his mind, initially an Orthodox church. Thus, the confessional belonging, although in the past, could be a reason for Barskiy to pay it more attention. The similar situation repeats with the Umayyads’ mosque in Damascus – for Barskiy it is the church of John the Baptist, turned into mosque, that’s why he is risking his life to get inside and to describe it.The traveler appreciates the regularity of architecture and clarity of its forms, which is demonstrated in his judgement about St Mamas monastery in Morphou on Cyprus he founds the most beautiful one in the island. At the same time, he is fascinated with very fine Gothic architecture of ruined Abbey of Bella Pais (also on Cyprus). Barskiy makes no difference between styles of architecture. Barskiy says that some of the buildings including Orthodox churches are ugly. There are buildings which are not regular, not decorated, destroyed and being destroyes ones. Consequently, his judgements tend to be free from religious and confessional belonging and the author aims for being objective.
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Galán Casado, Diego, Jaquina Castillo Algarra, and Bruno García Tardón. "Deporte e Inclusión social en personas con Trastorno Mental Grave (TMG)." Psychology, Society, & Education 12, no. 1 (March 9, 2020): 71. http://dx.doi.org/10.25115/psye.v0i0.2343.
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Las personas con Trastorno Mental Grave (TMG) pueden presentar estilos de vida poco saludables (Huizing et al., 2011), lo que redunda negativamente en su salud física y en la propia enfermedad. Conociendo que el ejercicio físico regular mejora tanto la salud física como el estado emocional y el bienestar personal (Mullor et al., 2017), nos planteamos investigar las consecuencias de un programa deportivo en personas con TMG. Para ello seleccionamos una liga denominada Ligasame, dirigida a personas con TMG integradas en diferentes recursos de rehabilitación psicosocial de la Red de Atención a Personas con Enfermedad Mental de la Comunidad de Madrid y Asociaciones de Familiares, por ser una experiencia consolidada el tiempo que integra a 15 equipos de fútbol. El objetivo de este trabajo es conocer las consecuencias de este programa de fútbol en las personas con TMG que participan en el mismo, a través de la percepción de 26 profesionales de Ligasame que trabajan para las asociaciones o recursos integrados en la misma. En esta investigación, con un diseño cualitativo emergente (Hernández, Fernández y Baptista, 2006), se analizaron 26 cuestionarios de respuestas abiertas, diseñado ad-hocpara el estudio, destinado a estos profesionales. Los resultados obtenidos muestran que un programa deportivo para personas con TMG mejora su condición física, favorece sus relaciones sociales, mejora su autoestima, reduce sus niveles de estrés y ansiedad y potencia aspectos transversales como la utilización de las nuevas tecnologías o la igualdad de género. Asimismo, ayuda a reducir el estigma que sufren estas personas, tanto socialmente como a nivel personal y familiar.
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Erbs, Philippe, Annie Findeli, Johann Foloppe, Juliette Kempf, Isabelle Farine, Baptiste Moreau, Julie Hortelano, Christelle Pichon, Jules Deforges, and Eric Quemeneur. "Abstract 6796: PoxSTG, a novel chimeric poxvirus with improved oncolytic potency." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6796. http://dx.doi.org/10.1158/1538-7445.am2023-6796.
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Abstract Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. We used a directed evolution process, pooling multiple species of orthopoxviruses to generate chimeric poxviruses with increased oncolytic properties. Through selective pressure by successive passages on human tumor cells, a new chimeric oncolytic poxvirus, named PoxSTG, was derived. The chimeric viral genome contains, in addition to sequences from several strains of Vaccinia virus, sequences of Rabbitpox virus and Cowpox virus. Compared with its parental viruses, PoxSTG has demonstrated superior oncolytic characteristics, and was notably attenuated in normal primary cells. PoxSTG has superior secretion of extracellular-enveloped virus (EEV) compared to all parental strains inducing higher dissemination of the virus into the tumors and more resistance to neutralization. PoxSTG was saved and showed potent antitumor effects in several syngeneic and xenograft mouse models of cancers. Furthermore, PoxSTG exerted low-dose antitumor effects in virus-injected and non-virus-injected distant tumors in a CRC xenograft model, demonstrating strong virus spread to distant tumors. All these data demonstrate the potential of PoxSTG as a novel therapeutic agent for cancer treatment. Citation Format: Philippe Erbs, Annie Findeli, Johann Foloppe, Juliette Kempf, Isabelle Farine, Baptiste Moreau, Julie Hortelano, Christelle Pichon, Jules Deforges, Eric Quemeneur. PoxSTG, a novel chimeric poxvirus with improved oncolytic potency. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6796.
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Chimthanawala, Abdequaem. "COVID-19: cases cured with Homoeopathy." International Journal of High Dilution Research - ISSN 1982-6206 20, no. 1 (March 28, 2021): 02. http://dx.doi.org/10.51910/ijhdr.v20i1.1077.
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Background: Homoeopathy is a medical science that should be practiced with evidence. As a practitioner, I was keen to show how Homoeopathy can give relief in this pandemic where conventional therapy was also struggling to offer treatment. Homoeopathic remedies given in Covid-19 cases in my OPD were prescribed to patients 1. who took only Homoeopathy, 2. who took Allopathy but got no relief and 3. hospitalized yet got relief with Homoeopathy. Few cases which did not get symptomatic relief were advised to stop treatment. Aims: To see the efficacy of Homoeopathy in treating covid 19 patients – with mild, moderate, and severe symptoms. Methodology: Data collected after permission from the patients to share case studies for Homoeopathy treatment of Covid-19 were obtained from GraceHealing Homeopathy clinic in Nagpur were categorized as mild to moderate and moderate to severe as per AYUSH guidelines; similimum with matching potency prescribed after detailed case inquiry, and regular Follow-ups were done until patients felt relief. Hypothesis: To see the action of Homoeopathy similimum - as a palliative, curative, and no action in treating covid-19 cases. Results: Homoeopathy has shown definite results in mild to moderate and moderate to severe cases up to 80% relief in mild to moderate 60% in moderate to severe. Mild to moderate cases where only Homoeopathy was given: China-ars, Ferrum-p, and Gelsemium were satisfactory. Baptisia and Carb-v adjuvant to Allopathy was also satisfactory. In hospitalized severe case gave relief, where Allopathy did not help. If Homoeopathy was given in such cases, it acts in increasing the immunity to make healing faster: Kali carb and Nux vomica satisfactory. Conclusion: With detailed case inquiry, symptomatic treatment with simillimum in correct potency can give Covid 19 patients relief.
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Wang, Aicheng, Kejun Mao, Tao Li, Lizhao Guan, Yuhong Chen, Haiting Dai, Xian Wu, et al. "Abstract 5609: A WRN screening cascade to facilitate novel drug discovery." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5609. http://dx.doi.org/10.1158/1538-7445.am2024-5609.
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Abstract Human RecQ deconjugating enzyme WRN is involved in DNA replication, DNA repair, recombination, transcription and telomere stabilization[1]. It plays a key role in nucleic acid metabolism as well. WRN defects lead to premature aging, type II diabetes, osteoporosis, atherosclerosis and cancer[2]. Hence it is of great interest of both pharmaceutical and academic field to develop the WRN inhibitors. Here we constructed an integrated experimental cascade, which contains both in vitro and in vivo assays, to conduct the high throughput hit-to-lead compound screen. WRN proteins of different length have been successfully purified and utilized to develop multiple biochemical assays such as unwinding assay and ATPase assay. We have also validated different cellular assays, including proliferation and immunofluorescence, to assess the cytotoxicity and the influence of downstream biomarkers of WRN inhibitors. A WRN knock-out cell line has been generated to better appreciate the inhibition mechanism. In addition, we have generated a WRN-HiBiT knock-in cell line to evaluate WRN degraders or target-compound interactions. Lastly, multiple CDX models utilizing different MSI or MSS cell lines have been validated to help determine the efficacy of WRN inhibitors thus shed light on the drug indications. Together our WRN screening cascade can provide comprehensive compound evaluation across in vitro and in vivo platforms, thus serve as an efficient screening platform for new drug discovery. [1] Kitano K. Structural mechanisms of human RecQ helicases WRN and BLM. Front Genet. 2014 Oct 29;5:366. [2]Hussain M, Krishnamurthy S, Patel J, Kim E, Baptiste BA, Croteau DL, Bohr VA. Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction. J Invest Dermatol. 2021 Apr;141(4S):968-975. Citation Format: Aicheng Wang, Kejun Mao, Tao Li, Lizhao Guan, Yuhong Chen, Haiting Dai, Xian Wu, Jiabao Lv, Xu Wang, Cong Huang, Tiejun Bing. A WRN screening cascade to facilitate novel drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5609.
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Smith, Margaret Rose, Yuezhu Wang, Ralph D’Agostino, Yin Lin, Jimmy Ruiz, Thomas Lycan, Umit Topaloglu, Mohammed Abdulhaleem, Michael Chan, and Fei Xing. "Abstract 952: Prioritizing mutations associated with smoking as a variable in lung cancer precision medicine with immunotherapies." Cancer Research 83, no. 7_Supplement (April 4, 2023): 952. http://dx.doi.org/10.1158/1538-7445.am2023-952.
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Abstract Background: In 2022, 230,000 new lung cancer cases will be diagnosed in the United States. The treatment regimen for non-small cell lung cancer (NSCLC) has drastically changed owing to the superior anti-cancer effects of immunotherapies. Immune checkpoint inhibitors (ICI) and chemo-immunotherapy (chemo-ICI) are the first-line treatments for NSCLC. Tumor Mutation Burden (TMB) and PD-L1 expression in tumor cells are potential biomarkers in predicting a patient’s survival and response to ICI. However, emerging data have shown that TMB and PD-L1 may no longer be an adequate biomarkers in predicting a patient’s response to ICI or chemo-ICI. We hypothesize that by using tumor-sequencing data and taking into effect a patient’s smoking status, we can identify biomarkers that predict survival to either ICI or chemo-ICI. Methods: To identify biomarkers, we collected genomic sequencing data and comprehensive clinical characteristics on 424 NSCLC patients who received ICI or chemo-ICI treatment at Atrium Health Wake Forest Baptist. Cox-proportional hazard regression models were fit to identify mutations that were “beneficial” (HR < 1) or “detrimental” (HR > 1) for patients on different treatment regimens, followed by the generation of mutation composite scores (MCS) for each treatment. Co-occurrence analysis was performed to identify novel co-occurring and mutually exclusive mutations in each treatment and smoking group by mutation interaction analysis. Results: We identify beneficial and harmful mutations in patients that received ICI or chemo-ICI treatment. We also identified unique biomarkers based on smoking statues. We then created an MCS for each smoking statues group and treatment type to assist personalize treatment. Future directions: We will validate these results in other institute cohorts and add other clinical characteristics to personalize treatment based on MCS for an individual patient. Citation Format: Margaret Rose Smith, Yuezhu Wang, Ralph D’Agostino, Yin Lin, Jimmy Ruiz, Thomas Lycan, Umit Topaloglu, Mohammed Abdulhaleem, Michael Chan, Fei Xing. Prioritizing mutations associated with smoking as a variable in lung cancer precision medicine with immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 952.
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Smith, Margaret R., Yuezhu Wang, Ralph D' Agostino, Yin Liu, Jimmy Ruiz, Thomas Lycan, George Oliver, et al. "Abstract 975: Treatment prognostic signature of patients with non-small cell lung cancer: a retrospective single-institutional study." Cancer Research 83, no. 7_Supplement (April 4, 2023): 975. http://dx.doi.org/10.1158/1538-7445.am2023-975.
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Abstract Introduction: Currently, several types of treatment can be used to treat non-small cell lung cancer (NSCLC) depending on a potential druggable mutation or stage of cancer. However, a limited number of biomarkers are available to guide clinicians in selecting the most effective therapy for all patients. Methods: The clinical characteristics of 642 NSCLC patients and tumor sequencing data were collected retrospectively at Atrium Health Wake Forest Baptist. Cox-proportional hazard regression models were fit to identify mutations that were “beneficial” (hazard ratio < 1) or “detrimental” (hazard ratio > 1) for patients on different treatment regimens, followed by the generation of mutation composite scores (MCS) for each treatment. The overall survival (OS) of patients receiving each treatment was plotted based on the patients’ MCS, and receiver operating characteristics (ROC) curves tested the predictive power of each MCS for each treatment group. We also identified novel co-occurring and mutually exclusive mutations in each treatment group by mutation interaction analysis. Results: We identified treatment-specific mutations associated with either a better or worse OS. The MCS generated for each treatment group significantly enhanced the prediction power compared to a single mutation with limited application in patients with rare mutations. Mutation signatures to chemotherapy (NTRK1, FBXW7, BRAF, MPL, KRAS, and GATA3) and immunotherapy (MAP2K1, EGFR, CDK4, NTRK1, and NOTCH1) have a comparable prediction power with actual clinical response. Conclusions: NSCLC patients’ responses to specific treatments are diverse because of tumor heterogeneity. Our work demonstrates how analyzing patients’ sequencing data facilitates the clinical selection of optimized treatment strategies. Citation Format: Margaret R. Smith, Yuezhu Wang, Ralph D' Agostino, Yin Liu, Jimmy Ruiz, Thomas Lycan, George Oliver, Umit Topaloglu, Jireh Pinkney, Mohammed N. Abdulhaleem, Michael D. Chan, Michael Farris, Jing Su, Fei Xing. Treatment prognostic signature of patients with non-small cell lung cancer: a retrospective single-institutional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 975.
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Хлюпина, А. А. "“Old Altars” of the Paris Opéra: The Fate of the Lullist Heritage in the 18th Century." Музыкальная академия, no. 1(785) (March 25, 2024): 72–91. http://dx.doi.org/10.34690/365.
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Еще в конце XVIII столетия в кругу французских литераторов сложилось негативное представление о консерватизме Парижской оперы. Оно было связано с уникальной по меркам европейских оперных театров того времени традицией регулярного возобновления сочинений Жана Батиста Люлли и Филиппа Кино, а также некоторых их преемников. Эта «старая музыка» («la musique ancienne») составляла основу оперного канона, который господствовал в стенах Оперы до 1770-х годов. Между тем, если внимательно рассмотреть практику оперных возрождений, то она оказывается важнейшей составляющей институциональной идентичности Королевской академии музыки, а не следствием неумелой репертуарной политики ее руководителей (как считалось долгое время). Постановщики десятилетиями тщательно редактировали оперное наследие, приспосабливали его к современной исполнительской практике и вкусам французской публики XVIII столетия, поддерживая при этом внешний налет консерватизма, приличествующего, по их мнению, академическому заведению. Таким образом им удавалось находить компромисс между несовместимыми на первый взгляд установками — сохранением классического репертуара (жизненно важного для функционирования Оперы) и его непрерывным обновлением, приведшим в конце столетия к радикальной стилевой трансформации «старой музыки», а затем и к окончательному отказу от нее. As early as the end of the 18th century, a negative view of the conservatism of the Paris Opéra was formed in the circle of French writers. It was associated with a tradition, unique by the standards of European opera houses of that time, of regular renewal of the works by Jean-Baptiste Lully and Philippe Quinault as some of their successors. This “old music” (“la musique ancienne”) formed the basis of the operatic canon, which dominated within the walls of the Opera until the 1770s. Meanwhile, considering the practice of opera revivals, it turns out to be a significant component of the institutional identity of the Royal Academy of Music—not the result of the inept repertory policy of its managers (as was believed for a long time). For decades the directors thoroughly edited the operatic heritage and adapted it to modern performing practice and the tastes of the French public of the 18th century, while maintaining a veneer of conservatism, befitting, in their opinion, an academic institution. In this way, they managed to find a compromise between seemingly incompatible principles—the preservation of the classical repertoire (vital for the functioning of the Opéra) and its continuous renewal, which led at the end of the century to the radical stylistic transformation of “old music,” and then to its final rejection.
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Glauser, Salome, Baptiste Ameline, Vanghelita Andrei, Dorothee Harder, Chantal Pauli, Marcel Trautmann, Wolfgang Hartmann, and Daniel Baumhoer. "Abstract 6218: NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well defined disease." Cancer Research 83, no. 7_Supplement (April 4, 2023): 6218. http://dx.doi.org/10.1158/1538-7445.am2023-6218.
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Abstract Background: Mesenchymal chondrosarcoma (MCS) is a high-grade sarcoma characterized by a biphasic histological appearance. However, more often than not, only the poorly differentiated component is present on a biopsy, thus more entities enter the differential diagnosis. Since the small cell component is morphologically non-specific, the differential diagnoses are broad, such as Ewing sarcoma, rhabdomyosarcoma, poorly differentiated synovial sarcoma small cell carcinoma, lymphoma and also melanoma. Morevoer, although the HEY1::NCOA2 gene fusion is present in almost all MCS, some studies have shown alternative alterations in the absence of the HEY1::NCOA2 fusion, suggesting genomic heterogeneity in at least a small subset of MCS. Thus, new diagnostic aids would be helpful to confirm the diagnosis. While most of the immunohistochemical profile overlaps between these tumours, NKX3.1 was recently proposed as a useful diagnostic marker for MCS. Furthermore, studies using DNA-methylation profiling show that MCS forms a distinct methylation cluster. The aim of this study is to evaluate the utility of these new diagnostic tools. Methods: Slides from 45 samples with MCS were stained with NKX3.1 antibody (EP356, Cell Marque, Roche) and were also investigated by methylome analysis (Mehylation Epic BeadChips, Illumina). Depending on tissue availability, the cases were subjected to HEY1::NCOA2 gene fusion testing. Results: The methylation profile showed a distinct cluster for mesenchymal chondrosarcoma, in line with the previous studies. Moreover, these findings were reproduced even when submitting tissue solely from one component, either the cellular or the cartilaginous one. In addition, the copy number profile derived from the methylome analysis proves its utility in distinguishing MCS from its mimics. On the other hand, only 32.6% of cases were positive for NKX3.1. Four samples initially diagnosed as MCS were histologically re-evaluated due to an atypical methylome profile, a high amount of CNV and/or lack of validation of the gene fusion. Methylation profiling led to the re-classification of three cases, whereas the fourth sample could not be further classified. Conclusions: We conclude that the methylation analysis, along with the copy number profile, are reliable tools in terms of diagnosing MCS. On the contrary, the immunomarker NKX3.1 shows contradicting results, proving itself as an unreliable marker in this setting. Citation Format: Salome Glauser, Baptiste Ameline, Vanghelita Andrei, Dorothee Harder, Chantal Pauli, Marcel Trautmann, Wolfgang Hartmann, Daniel Baumhoer. NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well defined disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6218.
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Brugat, Thibaut, Francesco Bergami, Baptiste Rugeri, Aurélie Janvier, Edith Steinberg, Luc Baron, Mandy Recolet, et al. "Abstract 4961: Novel biased PAR2 inhibitors with best-in-class properties reduce resistance to both chemotherapy and immunotherapy in oncology models." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4961. http://dx.doi.org/10.1158/1538-7445.am2023-4961.
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Abstract A large-scale meta-analysis has recently identified Protease-activated receptor 2 (PAR2) gene expression to be significantly associated with resistance to immune checkpoint blockade (ICB) in cancer patients and preclinical models. PAR2 and its ligands (proteases) are indeed upregulated in different cancer types and are expressed by various cells in the tumor microenvironment. In cancer cells, the PAR2 receptor controls cell migration, proliferation, survival, and expression of inflammatory cytokines. In immune cells, it influences the infiltration and phenotype of macrophages and T cells. Therefore, PAR2 represents a promising therapeutic target in oncology and immuno-oncology. A novel series of potent and selective PAR2 inhibitors has been developed at Domain Therapeutics. In vitro experiments demonstrated unique properties of our PAR2 small molecule antagonists when compared to those of competitors. The antagonists inhibit pathogenic signaling pathways (i.e. Gz, G13, Gq, G14 and G15 protein activation as well as intracellular calcium) but not βarrestin2 recruitment, potentially reducing the risks of drug resistance. Furthermore, they maintain high potency and insurmountability in conditions that mimic the tumor microenvironment (high concentration of proteases and acidic pH). Finally, their pharmacokinetic properties are compatible with a once-a-day oral administration and demonstrate no signs of in vivo toxicity except at high doses (>500 mg/kg). Proof-of-concept experiments showed that PAR2 antagonists prevented PAR2-mediated resistance to Gefitinib in vitro and increased the potency of anti-PD1 therapy in vivo in pre-clinical syngeneic mouse models. Immunohistochemistry analyses from cancer patient biopsies confirmed that high expression levels of PAR2 in cancer and stromal cells within the tumor microenvironment significantly associates with the patient overall survival. In conclusion, new potent and selective negative allosteric modulators of PAR2 have been developed, they demonstrate strong potency by alleviating the resistance to both chemo- and immunotherapy in cancer models. These findings confirm the high value of PAR2 as a therapeutic target and demonstrates the relevance of small molecule inhibitors targeting this receptor to treat cancer. Citation Format: Thibaut Brugat, Francesco Bergami, Baptiste Rugeri, Aurélie Janvier, Edith Steinberg, Luc Baron, Mandy Recolet, Xavier Wirth, Meriem Semache, Antoine Mousson, Camille Dietsch, Quentin Ruet, Orphée Blanchard, Célia Jacoberger-Foissac, Isabelle Cousineau, Maleck Kadiri, Anne-Laure Blayo, Christel Franchet, Stanislas Mayer, John Stagg, Nathalie Lenne, Stephan Schann. Novel biased PAR2 inhibitors with best-in-class properties reduce resistance to both chemotherapy and immunotherapy in oncology models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4961.
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Rodriguez, Julieta Elena, François Xavier Danlos, Alicia Larive, Aurelien Marabelle, Yohann Loriot, Caroline Robert, Laurence Albiges, et al. "Abstract 5068: Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5068. http://dx.doi.org/10.1158/1538-7445.am2024-5068.
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Abstract Introduction: Clonal Hematopoiesis of indeterminate potential (CHIP) is a clonal expansion of mutations affecting genes involved in hematologic malignancies in patients without a hematological disease per se. It has emerged as a significant risk factor for cardiovascular events via skewing innate immune cells towards a pro-inflammatory state. Recently studies have shown its potential detrimental impact on overall survival in patients treated with chemotherapy. However, its impact on patients treated with immune checkpoint blockers in monotherapy remains unclear. Objective: Our aim is to evaluate CHIP prevalence in a prospective cohort of patients treated with ICB for advanced solid tumors and its impact on patient outcomes. Materials and methods: We performed a Next-Generation Sequencing (NGS) panel of 74-genes dedicated to hematological alterations on DNA extracted from whole blood collected before first administration of an ICB for an advanced solid tumor, within the PREMIS trial (NCT03984318). CHIP prevalence was assessed according to a variant allele frequency (VAF) threshold ≥ 2%. Results: We included 127 pts in the analysis; 88 pts (69%) were male with a median age of 70 years [range 37-100]. Most common tumor locations were skin (29%), genitourinary (25%) and lung (19%). ICB setting was 1°L in 40% of patients; 2°L in 43%; > 3°L in 17%, and the most used ICB was Nivolumab in 39% of patients. At least 1 CHIP mutation was found in 55 pts (43%). The most frequent mutations were found in DNMT3A (40%), TET2 (18%) and PPM1D (13%). Co-mutations were found in 20% of patients. Median PFS was 7.7 months (m) for CHIPm patients compared to 5.7 m in non-CHIPm patients (p=2.2) and median OS was 16.2 m in CHIPm patients compared to 14.9 m in non-CHIPm patients (p= .5). No pts developed hematological disease during the follow up. Conclusion: CHIP is commonly found in pts with solid tumors, with a prevalence in our cohort of 43% with no statistical significance neither in PFS nor in OS in the CHIP-mutated population. Citation Format: Julieta Elena Rodriguez, François Xavier Danlos, Alicia Larive, Aurelien Marabelle, Yohann Loriot, Caroline Robert, Laurence Albiges, Maxime Frelaut, Mihaela Aldea, Benjamin Besse, Michel Ducreux, Caroline Even, Jean Baptiste Micol, Santiago Ponce, Christophe Marzac, Nathalie Chaput, Christophe Massard, Capucine Baldini. Clonal Hematopoiesis of indeterminate potential (CHIP) in patients with advanced solid tumors treated with immune checkpoint blockers (ICB) as monotherapy: Analysis of the PREMIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5068.
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Brugat, Thibaut, Maleck Kadiri, Samya Aouad, Anne-Laure Blayo, Baptiste Rugeri, Antoine Mousson, Aurélie Janvier, et al. "Abstract 684: DT-9045, a novel PAR2 inhibitor with best-in-class properties that reduces resistance to both EGFR-targeting therapies and immunotherapy in oncology models." Cancer Research 84, no. 6_Supplement (March 22, 2024): 684. http://dx.doi.org/10.1158/1538-7445.am2024-684.
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Abstract Protease-activated receptor 2 (PAR2) is a promising therapeutic target in oncology and immuno-oncology. It is upregulated and associated with poor prognosis in several cancer types. A pan-cancer meta-analysis showed that PAR2 is one of the genes most significantly associated with resistance to immune checkpoint blockade (ICB) and T cells dysfunction in cancer patients. Mechanistically, being expressed by various cells of the tumor microenvironment, PAR2 promotes both survival and proliferation of cancer cells and dampens the anti-cancer immune response. Domain Therapeutics has developed a novel PAR2 inhibitor, DT-9045, with best-in-class properties. Indeed, compared to its most advanced competitors, DT-9045 is a small molecule, orally bioavailable, insurmountable, biased, and active in tumor-like conditions (i.e. acidic pH and high level of activating proteases). This compound is also highly potent and selective on PAR2. Pharmacokinetic properties are suitable with a once-a-day oral administration. In vitro, DT-9045 completely prevented PAR2-mediated resistance to EGFR-targeting drugs. In vivo, its combination with anti-PD1 therapy showed a significant increase in efficacy over monotherapies in preclinical syngeneic mouse cancer models. This result was similar to the one observed in PAR2 knockout mice, indicating that oral administration of DT-9045 induces a complete inhibition of the receptor. We have further demonstrated that treatment with a PAR2 inhibitor enhances dendritic cell-mediated T cell activation and intratumoral infiltration of CD4+ and CD8+ T cells as well as a decrease in M2 macrophage infiltration. In conclusion, Domain Therapeutic has identified a novel PAR2 inhibitor, DT-9045, with clear competitive advantages. This preclinical candidate has shown strong potency in alleviating the resistance to both EGFR-targeting therapies and immunotherapy in preclinical cancer models. IND-enabling studies are currently ongoing to bring this new hope for cancer patients to the clinic. Citation Format: Thibaut Brugat, Maleck Kadiri, Samya Aouad, Anne-Laure Blayo, Baptiste Rugeri, Antoine Mousson, Aurélie Janvier, Edith Steinberg, Luc Baron, Mandy Recolet, Xavier Wirth, Maria Jesus Garcia-Leon, Quentin Ruet, Meriem Semache, Laurent Sabbagh, Orphée Blanchard, Christel Franchet, Stanislas Mayer, John Stagg, Nathalie Lenne, Stephan Schann. DT-9045, a novel PAR2 inhibitor with best-in-class properties that reduces resistance to both EGFR-targeting therapies and immunotherapy in oncology models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 684.
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Sauter, Camille, Thomas Morin, Fabien Guidez, John Simonet, Cyril Fournier, Céline Row, Denis Masnikov, et al. "Abstract 5588: Protein Arginine Methyltransferase 2 is involved in the control of inflammatory processes in acute myeloid leukemia." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5588. http://dx.doi.org/10.1158/1538-7445.am2024-5588.
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Abstract A direct link between chronic inflammation and development of Acute Myeloid Leukemia (AML) has been highlighted in the past few years, demonstrating an interconnection between marked inflammatory phenotype and aberrant myeloproliferation in AML patients. Treating AML patients exhibiting a higher inflammatory signature with anti-inflammatory molecules resulted in significant increase of overall survival. Protein Arginine Methyltransferases (PRMTs) are epigenetic factors known to regulate gene expression through methylation of histone tails. It has been previously reported that PRMT1, 4, and 5 inhibition exhibit anti-proliferative effects on AML models. In this study, we investigated the role of another PRMT, called PRMT2, in the development of AML through its regulatory roles in inflammatory pathways. We first determined from an AML cohort (The Leucegene project, IRIC, Montréal, QC, Canada) that patients with a low PRMT2 expression display an enrichment of proinflammatory pathways compared to patients with a high PRMT2 expression. Therefore, we hypothesized that PRMT2 could be a key regulator of inflammatory processes in AML. We thus used a PRMT2 knockout mouse model (Prmt2 KO) and a PRMT2 knockout human AML cell line to validate our hypothesis. Although we demonstrated no difference in the bone marrow progenitors or mature cell populations of Prmt2 KO mice compared to control, we observed that Prmt2 KO Bone-Marrow Derived Macrophages (BMDMs) are more sensitive to LPS stimulation and express higher levels of pro-inflammatory cytokines, supporting our previous findings for a role of PRMT2 in the negative regulation of inflammatory processes. PRMT2 depleted human AML cells displayed an increased pro-inflammatory signature due to overactivation of STAT3, which is caused by an enhanced activation of the NFkB signaling pathway, leading to an overproduction of IL6. Together, these findings demonstrate that PRMT2 is a key regulator of the control of inflammation in AML. Recognition of PRMT2 as a biomarker of inflammation in AML would help to adapt treatment possibly through the synergistic use of anti-inflammatory molecules with other cytotoxic drugs. Citation Format: Camille Sauter, Thomas Morin, Fabien Guidez, John Simonet, Cyril Fournier, Céline Row, Denis Masnikov, Baptiste Pernon, Anne Largeot, Aziza Aznague, Yann Herault, Guy Sauvageau, Marc Maynadie, Mary Callanan, Jean-Noël Bastie, Romain Aucagne, Laurent Levadny Delva. Protein Arginine Methyltransferase 2 is involved in the control of inflammatory processes in acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5588.
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Hart, Lowell L., and Magali Van den Bergh. "Abstract 3383: Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice." Cancer Research 83, no. 7_Supplement (April 4, 2023): 3383. http://dx.doi.org/10.1158/1538-7445.am2023-3383.
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Abstract PD-L1 testing via immunochemistry has become a widely used tool to predict response to immune checkpoint inhibitor (ICI) therapy in many tumor types. However this marker can be expressed heterogeneously, and can vary with time, treatment effects, and local factors including cytokine expression. Gene expression profiles of immunologically active genes are currently being studied to more accurately predict response to ICI treatment. To evaluate a potentially more straightforward way to accomplish this, we utilized an assay of cfRNA in plasma for PD-L1, utilizing a real-time PCR based assay (Circulogene, Inc, Birmingham, AL). The demonstrated limit of detection for PD-L1 RNA was 1 copy/ul. Results were reported as either not detected, or low at over 1%, or high at over 50%. We used the PCR 30th percentile Ct value corresponding to a tissue IHC PD-L1 of>50%, and the 66th percentile Ct value corresponding to a tissue PD-L1 expression of >1%. We then collected data on over 400 patients over a two year period at a large community oncology practice and at a university clinic (Florida Cancer Specialists and Atrium Health/Wake Forest-Baptist Comprehensive Cancer Center) who had a clinical necessity for molecular testing in a commercially available setting with a CLIA certified lab. In some cases the corresponding tissue PD-L1 testing was also available, and may have been either positive or negative.To date 41 patients have been found to have high levels of cfRNA for PD-L1. Their clinical course has been analyzed using the electronic medical record. Some patients have received standard of care therapy, and some have been given CPI therapy with or without chemotherapy, if the attending oncologist felt this to be the best palliative option. These include tumors such as CRPC, metastatic low grade neuroendocrine carcinoma and HR+ metastatic breast carcinoma, that have rarely been treated successfully with CPI therapy. Tumor types - all are stage IV solid tumor patients: 19 NSCLC, 7 breast carcinoma, 3 colorectal cancer, 3 castrate resistant prostate carcinoma, 9 other tumor types.Data collection for tumor response or clinical benefit on the 41 patients is ongoing and will be presented at the meeting, and compared to published CPI response data using standard tissue IHC testing. Citation Format: Lowell L. Hart, Magali Van den Bergh. Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3383.
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Marchand, Jean-Baptiste, Fadi Azar, Christelle Demeusoit, Patricia Kleinpeter, Jules Deforges, Fend Laetitia, Chantal Hoffmann, Huguette Schultz, Nathalie Silvestre, and Eric Quéméneur. "Abstract 694: TG6050 an oncolytic vaccinia virus armed with interleukin 12 and anti-CTLA4 antibody induces TME remodeling and strong anti-tumoral responses." Cancer Research 83, no. 7_Supplement (April 4, 2023): 694. http://dx.doi.org/10.1158/1538-7445.am2023-694.
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Abstract Background: By replicating specifically into tumor cells, oncolytic vaccinia viruses (VACV) can turn “cold” tumors “hot” while delivering therapeutic payloads into tumor. Thanks to its large genome capacity, multiple cloning loci, and availability of different promoters, VACV is an optimal vector for the design of advanced immunotherapies. Payloads with an established clinical efficacy but limited in terms of tolerability require local delivery. We report here the preclinical characterization of TG6050, a VACV encoding single chain interleukin 12 (IL12) and anti-CTLA4, targeting multiple cancer indications. Methods: TG6050 was generated by insertion of both the single chain IL-12p70, and an anti-CTLA-4 full-length (heavy and light chains independently) into the thymidine kinase (TK) and ribonucleotide reductase (RR) loci, of a triple deleted (ΔJ2R,ΔI4L,ΔM2L) VACV, Copenhagen strain. TG6050 was fully characterized in vitro, i.e. replication in tumor and normal cells, transgenes expression, functionality, and genetic stability. Its preclinical surrogate mTG6050, expressing murine payloads, was used to investigate the in vivo anti-tumoral activities in a broad range of immunocompetent murine models, as well as its mode of action in the reprograming of the tumor microenvironment (TME). Results: TG6050 displayed the same replicative, oncolytic activity, and genetic stability features as benchmark recombinant vaccinia viruses. IL-12 and anti-CTLA4 were both expressed at high levels, and as functional molecules by a broad panel of reference tumor cell lines. Local administration of mTG6050 induced accumulation of transgenes into tumor, with low systemic exposure. Noteworthy, expression of IL-12 did not accelerate the clearance of the viral vector. The combined effects of viral replication, IL-12 and anti-CTLA4 expression translated into impressive antitumoral activities in several syngeneic tumor models including immune-resistant ones such as B16F10 or LLC1. Transcriptomic analyses of the TG6050-treated tumors demonstrated a strong dynamic of infiltration by innate and adaptive immune cells. IFNy-ELISpot analysis on splenocytes confirmed induction of a strong systemic and specific anti-tumoral immune response. Moreover, the combination of TG6050 with ICI improved tumor regression in several challenging tumor models. Conclusion: TG6050 is a novel oncolytic VACV designed for multiple routes of administration, and several tumor indications. Its strong impact on the TME, by massive infiltration of innate and adaptive immune cells, translated into very remarkable therapeutic activities in resistant tumors. This anti-tumor activity was further enhanced by combination with anti-PD-1. Citation Format: Jean-Baptiste Marchand, Fadi Azar, Christelle Demeusoit, Patricia Kleinpeter, Jules Deforges, Fend Laetitia, Chantal Hoffmann, Huguette Schultz, Nathalie Silvestre, Eric Quéméneur. TG6050 an oncolytic vaccinia virus armed with interleukin 12 and anti-CTLA4 antibody induces TME remodeling and strong anti-tumoral responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 694.
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Loroña, Nicole C., Marco Matejcic, Daniel Sobieski, Nathalie T. Nguyen, Hannah J. Hoehn, Diana B. Diaz, Kritika Shankar, et al. "Abstract 6134: The Latino Colorectal Cancer Consortium: A resource for colorectal cancer disparities research." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6134. http://dx.doi.org/10.1158/1538-7445.am2024-6134.
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Abstract Purpose: The Latino Colorectal Cancer Consortium (LC3) was established to fill a gap in representation of the diverse Hispanic/Latino/a/x community in cancer genomic research and to enhance understanding of determinants of disparities in the burden of colorectal cancer (CRC). Methods: The LC3 joins together three established studies with deeply-annotated clinical, epidemiologic, and biologic data available for a heterogenous group of Hispanic/Latino/a/x men and women diagnosed with primary colorectal adenocarcinoma: the Hispanic Colorectal Cancer Study (California), the Total Cancer Care Protocol at Moffitt Cancer Center (Florida), and the Puerto Rico Biobank (southern Puerto Rico). Each contributing study collected data on demographics, medical history, family history, and lifestyle factors. Vital status, cause of death, treatment, and clinical characteristics were obtained through medical chart abstraction and/or linkage to cancer registries. Blood, saliva, or normal colonic tissues were used to extract and genotype germline DNA for a subset of participants. Tumor tissues (snap frozen or formalin-fixed paraffin-embedded) were evaluated by pathologists for diagnosis, tissue content, tumor cellularity, necrosis, immune infiltration, and additional histopathologic characteristics. Results: The LC3 has assembled 2,041 participants across the three studies to date, with recruitment ongoing. Median age at diagnosis is 57 (range: 19-93), 54% of participants are male, and 63% are colon cancer cases (vs. rectal cancer). Participants were diagnosed between 1999 and 2022. The target is to generate comprehensive multi-omic data on 600 LC3 participants. To date, 243 have genome-wide germline genotyping, 323 have paired tumor/normal whole exome sequencing, and 257 have T cell receptor immunosequencing (immunoSEQ, Adaptive Biotechnologies). Further, 206 cases are represented on a set of tissue microarray blocks (target N=281). Bulk RNA-seq data are to be generated on 250 tumors. Conclusions: The LC3 fills an important gap in research infrastructure for the scientific community. Key strengths of this unique consortium are its ability to capture a diversity of Latino CRC patients with respect to nativity and cultural heritage and to represent the spectrum of stages from early to metastatic. Ultimately, research from the LC3 will inform development of equitable precision medicine approaches and predictive models to improve the health of the rapidly-growing, heterogeneous Hispanic/Latino/a population. Citation Format: Nicole C. Loroña, Marco Matejcic, Daniel Sobieski, Nathalie T. Nguyen, Hannah J. Hoehn, Diana B. Diaz, Kritika Shankar, Esther Jean-Baptiste, Domenico Coppola, Clifton Fulmer, Ozlen Saglam, Kun Jiang, Teresita Muñoz-Antonia, Idhaliz Flores, Edna Gordian, José A. Oliveras Torres, Seth I. Felder, Julian A. Sanchez, Jason Fleming, Erin M. Siegel, Douglas Cress, Mariana C. Stern, Jamie K. Teer, Stephanie L. Schmit, Jane C. Figueiredo. The Latino Colorectal Cancer Consortium: A resource for colorectal cancer disparities research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6134.
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Peluso, Alexandra G., David I. Shalowitz, Scott Isom, Cheyenne R. Wagi, Aliza Randazzo, Derek Sean Falk, Kathryn E. Weaver, Ronny A. Bell, and Sarah A. Birken. "Loss to primary care provider follow-up among survivors five to seven years post-diagnosis." JCO Oncology Practice 19, no. 11_suppl (November 2023): 331. http://dx.doi.org/10.1200/op.2023.19.11_suppl.331.
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331 Background: Cancer survivors experience better outcomes when primary care providers (PCPs) are engaged in their care. Several studies indicate that nearly all survivors have ≥1 PCP visits per year in the initial five years post-diagnosis; however, little is known about sustained PCP engagement in survivors’ care. Our objective was to assess PCP engagement in survivors’ care 5-7 years post-diagnosis, and to characterize survivors who are most vulnerable to loss to PCP follow-up. Methods: We linked electronic health record ambulatory care visit data to Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFBCCC) registry data to identify survivors who were (1) ages ≥18 years, (2) diagnosed with a breast, colorectal, or uterine cancer between January 1, 2014 and December 31, 2015, (3) treated at AHWFBCCC as of September 1, 2019, and (4) had a PCP in the WF Health Network. We used multiple logistic regression to assess associations between survivor demographics, clinical factors, and healthcare utilization and odds of sustained PCP engagement in care, defined as having at least one ambulatory visit per year with a family or internal medicine provider. Results: There were 638 survivors who met our inclusion criteria. Of these, 122 died within the six-year post-diagnosis period and were excluded from analysis. Our analytic sample included 516 survivors who were primarily female (88.4%), white (75.0%), non-Hispanic (95.7%) stage 1 (50.6%) breast cancer survivors (69.2%) with a mean age of 60.7 years. Most (84.7%) survivors lived in an urban area at the time of diagnosis. In years 5-7 post-diagnosis, PCPs were engaged in care for 43% of survivors. Survivors with sustained PCP-engagement were on average 4.6 years older than those without (p<0.0001); survivors had 1.36 greater odds of having regular PCP visits for each decade increase in their age upon cancer diagnosis (p=0.0030). Survivors were less likely to be lost to PCP follow-up in if they were diagnosed at an earlier stage (p=0.0005) and had at least one visit annually with an oncologist 5-7 years post-diagnosis (p<0.0001). Conclusions: Sustained PCP engagement has been endorsed as critical by survivors, PCPs, and oncologists. In this study, we found that in the 5-7 years post-diagnosis, most (57%) survivors were lost to PCP follow-up. Older survivors, those currently engaged in oncology care, and survivors with earlier stage cancer were less likely to be lost to PCP follow-up, perhaps attributable to higher overall healthcare utilization. Our study may overestimate loss to PCP follow-up since we were unable to assess PCP visits outside of the AHWFB network; however, our findings offer evidence in support of calls for interventions to promote sustained PCP engagement among survivors, including the information, care coordination, and self-management support that survivors and PCPs have consistently reported needing for improved survivorship care and outcomes.
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Ay, Seha, Liang Liu, Elizabeth Forbes, Umit Topaloglu, and Wei Zhang. "Abstract 6126: Understanding disparities in lung cancer using single cell RNA sequencing data transformed by the Gerchberg Saxton algorithm." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6126. http://dx.doi.org/10.1158/1538-7445.am2024-6126.
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Abstract Purpose An overarching goal of this study is to reduce disparities in lung cancer research commonly manifested by racial and/or gender under-representations. By employing the Gerchberg-Saxton (GS) algorithm, we aim to diminish data noise/bias in single-cell RNA sequencing (scRNA-seq) gene expression data, thereby enabling more equitable research outcomes. An immediate goal is to remove extensive data bias associated with scRNA-seq data thus enhancing downstream Machine Learning analyses. Background: We have successfully applied the GS algorithm for fairer mortality rate predictions across different racial groups [1]. In this study, we seek to apply the GS algorithm to the scRNA-seq data that interrogate the cellular landscapes of lung cancer and the tumor microenvironment. Methodology: The application of the GS algorithm to single cell RNA data involved a series of steps. Initially, all data frames were transposed, switching columns and rows to represent gene expressions and single cells, respectively. The algorithm was then meticulously applied to each column, allowing for the uniform distribution of certain specific gene expression information across all single cells within the data frame. This column-wise application was crucial to maintain the integrity of individual cell characteristics while ensuring a fair structural distribution of gene expression data. The process aimed to balance the representation of genes across all cells, addressing inherent biases and noises in the original data structure. Data: The study utilizes a previously unpublished scRNA-seq dataset comprising 14 lung cancer patients from Wake Forest Baptist Comprehensive Cancer Center, including 6 African American and 8 Caucasian patients. Results: One out of 14 preliminary clustering results are presented in Figure 2 using ScanPy [2]. The initial findings are based on a restricted set of cell marker genes, which will be further developed with additional markers in subsequent analyses. With the application of the Gerchberg-Saxton algorithm, the Shannon Entropy [3] analysis revealed a more uniform randomness across gene expressions (Figure 1), and the unsupervised clustering indicated a clearer separation of cell types, significantly enhancing the ability for downstream analyses. The data transformation will be applied to the whole dataset for comparative analyses of cellular landscapes between lung cancer from different races and genders, to be reported at the AACR 2024 Annual Meeting. Conclusions: Our preliminary studies showed that the Gerchberg-Saxton algorithm is effectiveness in normalizing data distribution for scRNA-seq data, which has led to enhanced resolution of cell type differentiations in clustering analysis. With this refined methodology, we are better poised to better address lung cancer health disparities revealed by single cell sequencing analysis. Citation Format: Seha Ay, Liang Liu, Elizabeth Forbes, Umit Topaloglu, Wei Zhang. Understanding disparities in lung cancer using single cell RNA sequencing data transformed by the Gerchberg Saxton algorithm [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6126.
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Schmalz, Lauren, Cetin Urtis, Liang Liu, Elizabeth Forbes, Fang-Chi Hsu, Nury Steuerwald, Alberto de Hoyos, et al. "Abstract 5065: Integrating blood based liquid biopsies with TNM stage improves survival prediction model for non-small cell lung cancer." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5065. http://dx.doi.org/10.1158/1538-7445.am2024-5065.
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Abstract Introduction:Stage is the most important prognostic factor for survival in non-small cell lung cancer (NSCLC). The current TNM (Tumor, Node, Metastasis) staging system for NSCLC uses physical exam, histology, imaging, and surgical findings to define the extent and spread of a patient’s cancer. Despite advances in molecular testing which can impact treatment and prognosis for NSCLC patients, the current system does not incorporate molecular data into staging. We proposed a novel predictive model for survival analysis which integrates molecular analysis of liquid biopsies (B) into the TNM staging system (1). In this study, we tested this new staging system and our predictive model shows TNM + B (TNMB) provides a better predictive model for survival compared to TNM alone. Methods:176 patients were identified at Atrium Health Wake Forest Baptist with Guardant 360 liquid biopsies sent at diagnosis for NSCLC. Clinical data was obtained through retrospective chart review. Molecular analysis was performed on 81 genes across all Guardant 360 liquid biopsies. Using Cox proportional hazards model, we identified significant gene mutations or genes with significant magnitude of variant allele frequency (VAF) that improved survival prediction. We then designed a novel staging system incorporating whether a patient had a positive liquid biopsy test (B1), defined by the presence of these impact gene variables, to TNM stage. Results: Three impact genes STK11 (p=0.0253), NFE2L2 (p = 0.0025), TP53 (p=0.0129) and one gene with a magnitude of VAF, ARID1A (p=0.0082) was identified which significantly improved the predictive model for survival. Patients with negative liquid biopsy test, B0, had improved survival compared to patients with a positive liquid biopsy test, B1 (p<0.005). In our cohort, TNM staging alone did not show a significant survival difference between stage II and III (p = 0.19). Whereas TNMB staging showed a significant survival difference between stage II, III and IV. Conclusions: While TNM stage remains a major prognostic factor for NSCLC patients, it fails to incorporate molecular data which has a critical impact on management and prognosis. We designed a novel method to analyze molecular data obtained by liquid biopsy to identify significant gene mutations and gene magnitude of VAF that impacts survival prediction. In our cohort, we showed 4 impact genes which we used to create a new TNMB staging system which led to improved survival prediction compared to TNM alone. Acknowledgments: Research partly supported by NIH T32 Grant (T32CA247819) and Cancer Center Support Grant (P30CA012197) Reference: (1) Yang M, Forbes ME, Bitting RL, O'Neill SS, Chou PC, Topaloglu U, Miller LD, Hawkins GA, Grant SC, DeYoung BR, Petty WJ, Chen K, Pasche BC, Zhang W. Incorporating Blood-based Liquid Biopsy Information into Cancer Staging: Time for a TNMB System? Ann Oncol. 2018 Feb 1;29(2):311-323. Citation Format: Lauren Schmalz, Cetin Urtis, Liang Liu, Elizabeth Forbes, Fang-Chi Hsu, Nury Steuerwald, Alberto de Hoyos, Thomas Lycan, Jimmy Ruiz, William Petty, Wei Zhang. Integrating blood based liquid biopsies with TNM stage improves survival prediction model for non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5065.
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Tagliamento, Marco, Christophe Marzac, Mihaela Aldea, Damien Vasseur, Arnaud Bayle, Anas Gazzah, Maud Ngocamus, et al. "Abstract 4526: Molecular landscape of clonal hematopoiesis in patients with lung cancer: First results of the CHIC study." Cancer Research 83, no. 7_Supplement (April 4, 2023): 4526. http://dx.doi.org/10.1158/1538-7445.am2023-4526.
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Abstract Introduction: CHIC (Clonal Hematopoiesis In Lung Cancer) is a retro-prospective study that aims to describe the characteristics of clonal hematopoiesis (CH) in patients with non-small cell lung cancer (NSCLC). We present preliminary results from the retrospective cohort. Experimental procedures: A retrospective analysis conducted in patients with metastatic or recurrent NSCLC included in the MATCH-R study (NCT02517892) at Gustave Roussy (Villejuif, France). CH was evaluated by a 74-gene targeted NGS panel (HaloPlex - Agilent) performed on DNA extracted by isolated-by-blood leukocytes. The variant allele frequency (VAF) threshold of detection was set at 1%. Results: 108 consecutive patients with advanced NSCLC included from October 2015 to July 2019 were evaluated, irrespective of the tumor molecular profile. 46% of the patients were female, 67% were former or current smokers. 82% of the patients had adenocarcinoma and 44%, 23%, 33% had bone, liver and/or brain metastases, respectively. Patients had received a median of 2 lines of systemic therapy and 81% were on active anticancer treatment at the time of CH assessment. At least one CH mutation was found in 38 out of 108 patients (35% prevalence), with an increasing with age trend. Patients carrying CH were older as compared to those without CH and had in 29% vs. 11% of cases tumor histology other than adenocarcinoma (p=0.009). No difference in overall survival was observed according to CH detection (log rank p=0.318). We found 64 mutations in 19 different genes: 63% of the patients carried a single mutation, while co-occurrence of two, three, four or five mutations, within the same gene or in more than one, was found in seven (18%), four (11%), one (3%) and two patients (5%), respectively. Epigenetic modifiers (DNMT3A, TET2, ASXL1) were the most frequently mutated genes: 38 mutations with a median VAF of 6.5% detected in 32 patients. DNA repair genes (PPM1D, TP53, CHEK2, ATM) were the second most frequently mutated: 11 mutations at a median VAF of 4% were detected in 9 patients. 7 mutations in genes encoding for the cohesin complex (SMC3, SMC1A, RAD21, STAG2) were found in 6 patients, with a median VAF of 5%. A non-simultaneous cfDNA sequencing by FoundationOne Liquid CDx assay (324-gene panel) was performed in 9 patients for tumor profiling. In 2 out of 3 tested cases the presence of CH was confirmed in plasma liquid biopsy. 4 patients with no detectable CH by the targeted blood sequencing subsequently were found having CH mutations in plasma NGS, on average 45 months apart. To note, as many as 5 out of the 19 detected mutated genes (PPM1D, SMC3, SMC1A, PRPF8, ZRSR2) are not part of the FDA-approved NGS panel used for cfDNA profiling in solid tumors. Conclusion: We found a consistent prevalence of CH in patients with NSCLC by using a sequencing approach targeted for hematologic disorders. Prognostic implications of CH are under investigation and will be evaluated in the full cohort. Citation Format: Marco Tagliamento, Christophe Marzac, Mihaela Aldea, Damien Vasseur, Arnaud Bayle, Anas Gazzah, Maud Ngocamus, Claudio Nicotra, Julieta Rodriguez, Antonin Levy, Capucine Baldini, Santiago Ponce, Felix Blanc-Durand, Etienne Rouleau, Antoine Italiano, Ludovic Lacroix, Luc Friboulet, David Planchard, Fabrice Barlesi, Yohann Loriot, Jean-Baptiste Micol, Benjamin Besse. Molecular landscape of clonal hematopoiesis in patients with lung cancer: First results of the CHIC study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4526.
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Marchand, Jean-Baptiste, Elodie Pintado, Marshall Dunlop, Christelle Remy, Patricia Kleinpeter, Shirley Shön, Fend Laetitia, et al. "Abstract 1885: Selection of an optimal anti-PD-L1 single domain antibody format for the vectorization into oncolytic vaccinia virus and the generation of bispecific immunomodulators." Cancer Research 83, no. 7_Supplement (April 4, 2023): 1885. http://dx.doi.org/10.1158/1538-7445.am2023-1885.
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Abstract Background: Single domain antibodies (sdAbs) isolated after immunization of camelids are particularly attractive formats for their high modularity and small size allowing a better diffusion into tumors. However, the short in vivo half-life of sdAbs, related to the lack of a Fc domain, limits their clinical application. By replicating specifically into tumor cells, the oncolytic vaccinia virus (VACV) is an optimal vector to deliver and maintain high intra-tumoral concentrations of therapeutic sdAb. Moreover, sdAb targeting immunological targets, such as PD-L1, may synergize the anti-tumoral activity of VACV. Randox and Transgene report the selection and characterization of a sdAb targeting the human PD-L1 and the design of optimal formats, including bispecific anti-PD-L1-CD40 ligand, for vectorization into VACV. Methods: Alpacas were immunized with human PD-L1 protein and sdAb coding sequences were isolated by PCR. Anti-PD-L1 sdAb binders were selected by phage display and sdAb blockers of PD-L1/PD-1 interaction were identified by ELISA. The ability of the selected sdAb to disrupt the PD-L1/PD-1 interaction was verified on transformed and primary cells. To fine-tune an optimal anti-PD-L1, several sdAb formats were designed and vectorized into VACV. The sdAb format exhibiting the best PD-L1/PD-1 blocking activity was selected by the screening of culture supernatants of several VACV-sdAb infected tumor cells. Finally, anti-PD-L1 sdAb-CD40L fusions were designed to generate a strong CD40 agonist active only in a PD-L1 positive environment. Results: SdAb clone 1A1 exhibited the best PD-L1/PD-1 blocking activity which remained unchanged after extensive humanization (latterly becoming named GS542). GS542 was vectorized in VACV as monomeric single chain homodimer, and fused to Fc domain or antibody hinge domain to foster dimerization together with full length IgG1 avelumab as anti-PD-L1 benchmark. All constructs were expressed by infected tumor cells. The single chain homodimer displayed the best PD-L1/PD-1 blocking activity, superior to that of avelumab. Moreover, GS542-CD40L fusions were designed to take advantage of the natural trimerization of CD40L to increase the avidity for PD-L1 while clustering CD40L at the surface of PD-L1+ cells to trans-activate the CD40 pathway. Evaluation of these GS542-CD40L fusions showed strong CD40 agonist activity depending on the presence of PD-L1+ cells making these constructs safer CD40 agonists. Conclusion: An anti-PD-L1 sdAb with a strong blocking activity was selected, humanized and evaluated under different VACV-vectorized formats. The single chain homodimeric sdAb expressed by VACV was identified as the best PD-L1/PD-1 blocking format. Furthermore, bispecific anti-PD-L1 sdAb-CD40L fusions that exhibited strong CD40 agonist activity was charactered within a PD-L1+ environment. Citation Format: Jean-Baptiste Marchand, Elodie Pintado, Marshall Dunlop, Christelle Remy, Patricia Kleinpeter, Shirley Shön, Fend Laetitia, Renée Brandely, Delphine Suhner, Eline Winter, Nathalie Silvestre, Claire Huguet, Peter Fitzgerald, Eric Quéméneur. Selection of an optimal anti-PD-L1 single domain antibody format for the vectorization into oncolytic vaccinia virus and the generation of bispecific immunomodulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1885.
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Siegel, Erin M., Jacob K. Kresovich, Amanda M. Bloomer, Anders Berglund, Esther Jean-Baptiste, Gillian Trujillo, Rachel Carmella, et al. "Abstract 7017: Increased epigenetic age acceleration in young adult and early onset colorectal cancer patients post-treatment: A ColoCare Pilot Study." Cancer Research 84, no. 6_Supplement (March 22, 2024): 7017. http://dx.doi.org/10.1158/1538-7445.am2024-7017.
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Abstract Introduction: Advanced biological age relative to chronological age has been observed in individuals with colorectal cancer (CRC), and there is growing evidence that cancer treatments can further accelerate biological aging. However, the influence of age at diagnosis on these relationships has yet to be examined in detail. This pilot study used data from the ColoCare Study to explore pre- and post-treatment differences in age acceleration by chronological age at CRC diagnosis. Methods: The ColoCare Study is a prospective cohort study of newly-diagnosed CRC patients enrolled across seven U.S. and European sites. Participants in this pilot study were from the ColoCare site in Tampa, Florida who had available pre-treatment blood DNA. Young adult (YA, aged 18-39) and early onset (EO, aged 40-49) participants were matched with average onset (AO, aged 50-64) and late onset (LO, aged >64) participants on stage, sex, race and microsatellite instability status. Genome-wide DNA methylation profiles were assayed on buffy coat DNA using MethylationEPIC v2 BeadChips. PhenoAgeAccel and GrimAgeAccel were calculated on all samples to quantify the difference between DNA methylation-predicted biological age and chronological age (i.e., age acceleration). Linear regression models were used to estimate the associations of age at diagnosis and treatment with PhenoAgeAccel and GrimAgeAccel, adjusted for sex, race, and site (rectal, colon). Results: The sample (n=60) included n=19 YA, n=15 EO, n=11 AO, and n=15 LO participants with pre-treatment blood DNA. Over half (n=15 YA/EO, n=20 AO/LO) had a paired post-treatment blood sample available. Half of participants were female and had colon tumors, and 76% were diagnosed with stage I-III disease. Pre-treatment, PhenoAgeAccel and GrimAgeAccel were similar across age groups (P > 0.05). In the subset of participants with pre- and post-treatment samples, age acceleration appeared to increase post-treatment (pre- and post-treatment differences, PhenoAgeAccel: 1.44, SD: 5.55, P= 0.13; GrimAgeAccel: 0.92, SD: 2.80, P= 0.06). Increases were largest among YA/EO participants. In adjusted models, the predicted differences in pre-to post-treatment PhenoAgeAccel were 2.89 (95% CI: -0.13, 5.90) in YA/EO and 0.36 (95% CI: -2.25, 2.96) in AO/LO (P-difference= 0.20). The predicted differences in GrimAgeAccel were 1.75 (95% CI: 0.25, 3.25) in YA/EO and 0.30 (95% CI: -1.00, 1.60) in AO/LO (P-difference= 0.15). Conclusions: In this pilot study of CRC patients, pre-treatment age acceleration did not vary by age at diagnosis. Post-treatment, patients diagnosed at age 49 or younger had larger increases in age acceleration than patients diagnosed at age 50 or older. These findings warrant further investigation in larger samples and to determine if increases in post-treatment age acceleration as associated with patient outcomes and treatment response. Citation Format: Erin M. Siegel, Jacob K. Kresovich, Amanda M. Bloomer, Anders Berglund, Esther Jean-Baptiste, Gillian Trujillo, Rachel Carmella, Julaxis Love, Seth Felder, Jennifer Ose, Biljana Gigic, Christopher I. Li, Jane C. Figueiredo, Adetunji T. Toriola, Cornelia M. Ulrich, David Shibata, Laura B. Oswald. Increased epigenetic age acceleration in young adult and early onset colorectal cancer patients post-treatment: A ColoCare Pilot Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7017.
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Vibert, Julien, Clémence Hénon, Lambros Tselikas, Baptiste Bonnet, Arnaud Pagès, Alice Bernard-Tessier, Léo Colmet-Daage, et al. "Abstract 6406: Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal single-cell analysis of patient tumors identifies biological correlates of response to PARP inhibitors and anti-PD-L1 therapy." Cancer Research 84, no. 6_Supplement (March 22, 2024): 6406. http://dx.doi.org/10.1158/1538-7445.am2024-6406.
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Abstract Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have immunomodulatory properties that may potentiate anti-PD-L1 therapy. To explore this, we developed the academic ARIANES phase 2 basket trial, which evaluated the PARPi rucaparib (R) and the anti-PD-L1 atezolizumab (A) in selected patients (pts). We performed single-cell RNA + T cell receptor sequencing (scRNA+TCR-seq) on 3 sequential tumor biopsies in a pts subset. Methods: ARIANES comprised 4 molecularly-selected DNA damage response deficient (DDRd), 3 platinum-sensitive, and 2 unselected cohorts of pts with non-small cell lung (NSCLC), prostate (CRPC), and other non-breast non-ovarian cancers. R was administered for 3 weeks, followed by R+A. Primary endpoint was overall response rate (ORR) at 12 weeks per cohort. scRNA+TCR-seq was performed on fresh biopsies collected at baseline, on R, and on R + A in the same lesion, with concomitant plasma collection. We tracked the evolution over time of tumor and microenvironment cells, differentially expressed genes and signatures within each cell population, and TCR clonal dynamics. Results: ARIANES enrolled 130 pts, including 27 DDRd CRPC and 3 DDRd NSCLC pts, on which we focus here. Best ORR by RECIST v1.1 was 22% (6/27) in CRPC pts, and mPFS: 7.9 months (95% CI 4 - 11.1) at data cut-off. ORR was 0% in NSCLC pts. We successfully profiled 3 sequential fresh biopsies in 2 BRCA2-mutant CRPC, 1 ATM-mutant, and 1 RAD54L-mutant NSCLC pts. Tumor, T and B lymphoid, myeloid, plasma, dendritic, NK, endothelial, and stromal cells were identified in all samples. Differential expression testing unveiled PARP1 upregulation in tumor cells on R. One CRPC pt with prolonged partial response displayed activation of innate immune sensing pathways (including cGAS-STING and IFN signaling) in tumor and immune cells, as well as JAK/STAT and CCL5, all increasing gradually on R and R + A; scTCR-seq revealed the expansion of specific T cell clonotypes on R + A. One ATM-mutant NSCLC pt with 6-month stable disease displayed increased cGAS/STING, JAK/STAT and CCL5 activation on R in NK cells only, and no TCR expansion. None of the above was observed in the 2 pts who progressed. Complete clinical and translational study results will be presented at the congress. Conclusion: Sequential scRNA+TCR-seq enables the dynamic assessment of tumor and immune cells on therapy. Our data confirms the potential of R to activate innate immune pathways in pt tumors, and R + A to induce T cell activation and clonal expansion. To our knowledge, this is the first study providing a longitudinal single-cell resolution analysis of the clonal evolution of tumor and immune cells in pts on PARPi + anti-PD-L1. We identify potential biological correlates of therapy response, including the activation of innate immune pathways and TCR expansion. Citation Format: Julien Vibert, Clémence Hénon, Lambros Tselikas, Baptiste Bonnet, Arnaud Pagès, Alice Bernard-Tessier, Léo Colmet-Daage, Roman Chabanon, Nicolas Dorvault, Clémence Astier, Anas Gazzah, Aurore Jeanson, Aurélien Parpaleix, Ronan Flippot, Natacha Naoun, Anna Patrikidou, Pernelle Lavaud, Giulia Baciarello, Emeline Colomba, Alina Fuerea, Laurence Albiges, Christophe Massard, Santiago Ponce, Yohann Loriot, Stéphane Champiat, Capucine Baldini, Fanny Bouquet, Nathalie Droin, Karim Fizazi, Damien Vasseur, Patricia Martin-Romano, Etienne Rouleau, Kaïssa Ouali, Sophie Postel-Vinay. Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal single-cell analysis of patient tumors identifies biological correlates of response to PARP inhibitors and anti-PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6406.
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Montes, D., C. A. Hulshizer, E. Myasoedova, J. M. Davis, A. Hanson, A. Duarte-Garcia, G. Figueroa-Parra, B. Chevet, and C. S. Crowson. "POS0038 UTILIZATION OF CARDIOVASCULAR PREVENTIVE SERVICES IN A RHEUMATOID ARTHRITIS POPULATION BASED COHORT." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 228.1–228. http://dx.doi.org/10.1136/annrheumdis-2023-eular.4184.
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BackgroundRheumatoid arthritis (RA) increases the burden of cardiovascular disease (CVD). Fasting blood glucose, fasting lipoprotein profiles, and blood pressure measurements are recommended at regular intervals to screen for classical CVD risk factors of diabetes mellitus (DM), hyperlipidemia (HLD), and hypertension (HTN), respectively.ObjectivesOur objectives were 1) to perform a contemporary assessment of the trends of CVD preventive service utilization in patients with RA compared to matched non-RA comparators, 2) identify RA patient characteristics that may influence trends in preventive services utilization, and 3) assess how a diagnosis of RA alone influences approaches to CVD prevention compared to the other classical CVD risk factors.MethodsInpatient and outpatient medical records for each potential case were manually reviewed. All incident patients fulfilled the 1987 American College of Rheumatology (ACR) classification criteria for RA or the 2010 European League Against Rheumatism (EULAR)/ American College of Rheumatology (ACR) criteria. All ≥19-year-old patients with an RA diagnosis living in an 8-county region on January 1, 2015 (index date), were included and matched (1:1) by sex, age, and county to non-RA comparators. Rates of screening for the classical CVD risk factors were compared between groups using Cox models with adjustment for age, sex, and race.ResultsDM screening was more common among patients with RA ([HR] 1.10, 95% CI 1.01–1.19), as was HTN screening ([HR] 1.37, 95% CI 1.24–1.52). However, HLD screening in RA was similar to comparators ([HR] 0.99, 95%CI 0.89–1.10). RA patient characteristics that influenced classical CVD risk factor screening included: smoking history, obesity, RA duration of < 5 years, older age at the time of RA diagnosis, a higher Charlson comorbidity index, the use of >90 days of glucocorticoid therapy before the index date, the use of disease modifying anti-rheumatic drugs before the index date, and living in the lowest quartile of the Area Deprivation Index within our cohort. Lastly, patients with RA and no classical CVD risk factors had a lower probability of undergoing DM ([HR] 0.67, 95% CI 0.57–0.78) and HLD screening ([HR] 0.65, 95% CI 0.54–0.79) than non-RA patients with one classical CVD risk factor diagnosis. HTN screening was similar between both groups ([HR] 1.01, 95% CI 0.83–1.23).ConclusionRA patients undergo CVD preventive screening at rates at least comparable to the general population. However, despite the equivalent-to-higher CVD risk, RA does not appear to be approached as aggressively as traditional CVD risk factors. (1,2) These findings demonstrate an opportunity to improve RA patient care. While EULAR provides guidance for stratifying CVD risk in patients with inflammatory joint disease, there is no equivalent guidance from American medical bodies. (3) Given our findings, clinical practice in the United States could benefit from establishing such recommendations. These recommendations should be forceful in framing RA as conferring an equivalent-to-higher CVD risk as the classical CVD risk factors.Table 1.Cumulative Incidence of Screenings5-year Cumulative Incidence, (95% CI)All RA PatientsAll Non-RA PatientsHRDM Screening94.0% (92.6 – 95.3)93.8% (92.4 – 95.2)1.10 (1.01 – 1.19)HTN Screening99.1% (98.5 – 99.8)96.3% (95.0 – 97.6)1.37 (1.24 – 1.52)HLD Screening74.3% (71.5 – 77.1)75.2% (72.5 – 78.1)0.99 (0.89 – 1.10)RA w/o CVD Risk FactorsNon-RA w/ only 1 CVD Risk FactorHRDM Screening RA w/o CVD Risk Factors = 477 Non-RA, Only 1 CVD Risk Factor (HTN or HLD) = 38291.9% (88.8 – 95.1)98.9% (98.0 – 99.9)0.67 (0.57–0.78)HTN Screening RA w/o CVD Risk Factors = 579 Non-RA, Only 1 CVD Risk Factor (HLD or DM) = 16099.6% (99.2 – 100)99.0% (97.0 – 100)1.01 (0.83–1.23)HLD Screening RA w/o CVD Risk Factors = 579 Non-RA, Only 1 CVD Risk Factor (HTN or DM) = 24871.3% (67.1 – 75.8)84.9% (78.7 – 91.6)0.65 (0.54–0.79)CI: confidence interval; HR: hazard ratioReferences[1]Liao KP., Rheumatology (Oxford). 2013[2]Solomon DH., Ann Rheum Dis. 2006[3]Agca R., Ann Rheum Dis. 2017Acknowledgements:NIL.Disclosure of InterestsDaniel Montes: None declared, Cassondra A Hulshizer: None declared, Elena Myasoedova: None declared, John M Davis III Grant/research support from: Pfizer, Andrew Hanson: None declared, Ali Duarte-Garcia: None declared, Gabriel Figueroa-Parra: None declared, Baptiste Chevet: None declared, Cynthia S. Crowson: None declared.
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Freire Carrillo, Victor Hugo, and Fredy Leonard Ibarra Sandoval. "Strategic marketing to strengthen dairy production." Universidad Ciencia y Tecnología 25, no. 111 (December 11, 2021): 154–64. http://dx.doi.org/10.47460/uct.v25i111.526.
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Microenterprises that produce dairy products face problems of unfair competition, unfavorable government regulations, and under-utilization of milk derivatives. This work focuses its objective on analyzing and developing strategic marketing for the strengthening of dairy production; For this, the contributions of marketing and its relationship with dairy production are enunciated and the marketing strategies of applied products are analyzed. Through a qualitative approach, with quantitative data, in the light of a descriptive, cross-sectional method, the methodological process is developed, through which results are obtained that show the need to propose product strategies and take advantage of serum waste milk. In this sense, the elaboration of products derived from whey is proposed for their subsequent commercialization. As a conclusion, small economy companies cannot afford investments of more than 800,000.00 USD; therefore, they require alternatives such as associativity.
Keywords: strategic marketing, product strategies, dairy, whey.
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Macuka, Jekaterina. "THE MODEL OF RELATIONS BETWEEN THE STATE AND RELIGIOUS ORGANIZATIONS AND ITS IMPLEMENTATION IN THE REPUBLIC OF LATVIA." Via Latgalica, no. 2 (December 31, 2009): 63. http://dx.doi.org/10.17770/latg2009.2.1608.
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Models of relations between the state and religious organizations and the basic principles of their implementation are analyzed with the aim to determine which model of relations is being realized in the Republic of Latvia as well as to establish whether a model of relations, secured by a normative act, corresponds to the one implemented in practice. Within this work, the method of analysis has been used when considering the models of relations between the state and religious organizations, as well as the comparative method in the comparison of application of the basic principles of these models in the Republic of Latvia. The relations between the State and religious organizations are examined from the administratively legal and constitutionally legal aspect. The normative acts of the Republic of Latvia are discussed, as well as their mutual interaction and the collisions having sprung up between them. Laws and regulations of the Republic of Latvia are evaluated in connection with the norms of other European Union Member States, which regulate the relations between the state and religious organizations, and their experience. Evaluating the practice of other countries and the implemented models of relations between the state and religious organizations monographs and scientific papers by the scientists of the respective countries have been used. The content of international legal norms regulating freedom of religion have been analyzed as well as the requirements of the normative acts of the Republic of Latvia and their interaction. As grounds for conclusions, rulings by the court are chosen in cases where the application of legal norms is adjudicated concerning the realization of the right to the freedom of religion. Three fundamental principles are pointed out in the research basing on which the relations between the state and religious organizations are formed: association between the state and religious organizations, cooperation between the state and religious organizations and segregation between the state and religious organizations. Basing on the abovementioned principles, all models of relations between the state and religious organizations are formed. The model being implemented in a state can be determined by the regulation of the activity of religious organizations ensured with normative acts, by the range of rights of religious organizations, by peculiar features of preconditions, by the range of privileges, and by the burden of responsibilities imposed on religious organizations. To a large extent, the model of relations between the state and religious organizations depends on state traditions, historical development, distribution and impact of the definite religion within the state territory. The principle of unity between the state and religious organizations indicate the unity between them, institutions of religious organizations are identified as state institutions. Implementation of the abovementioned principle can manifest as an absolute unity between the state and church when state laws are based on definite religious norms and, in case of collisions, the principles of religious doctrine are applied. Or, within the abovementioned principle, two models of relations can be distinguished: a model of religious state and a model of state religion (church). The principle of cooperation between the state and religious organizations provides for separation of the state and religious organizations, they are functioning as autonomous subjects, religious organizations form their own structure and define their inner administration, the state on its part does not interfere in the inner affairs of religious organizations. Nevertheless, the state and religious organizations cooperate in order to achieve definite aims. Such a model of cooperation can be called the model of cooperation. In countries where the principle of separation of the state and religious organizations is in force and the model of segregation is functioning, the autonomy of religious organizations and the state are strictly separated. Each of these subjects is functioning in its own sphere, in parallel to one another. Religious organizations are not vested the rights to perform the functions of the state, and they do not receive financial support. Registration of a religious organization is the starting point where the activities of the state and of religious organizations come into contact. Registration of a religious organization is a basis for the model of relations between the state and religious organizations to be implemented in the given country. In the Republic of Latvia, the process of registration of religious organizations is regulated by the Law on Religious Organizations which provides for the order of registration of religious organizations as well as the legal status of the religious organizations to be registered; registration has a multi-stage structure. Initially, a congregation is registered as reregistrable, but later it acquires a regular status and after uniting the congregations can form a religious union (church). Religious unions (churches) have the right to establish dioceses and institutions. The next step in the mentioned chain includes religious organizations whose relations with the Republic of Latvia can be regulated by special laws. The State has established special relations with Evangelical Lutheran, Roman Catholic, Orthodox, Old Believer, Methodist, Baptist, Seventh-day Adventist and Moses faith (Judaist) denominations. These denominations have a peculiar status in the Republic of Latvia, the range of their rights differs from the rights of other congregations. Relations between the religious unions (churches) of these denominations and the State are regulated by special laws that define their rights and status. The Latvian Constitution (Satversme) contains a reference to the model of relations between the Republic of Latvia and religious organizations providing that the State is separated from the church. Evaluation of the features of a model of separation and its application to the relations between the Republic of Latvia and religious organizations allows to determine whether the implemented model is a model of separation or whether the relations between the State and religious organizations realized in practice belong to quite another model. The requirement for autonomy of religious organizations and the State can be regarded as satisfied, since the demand for non-interference by the State in the inner activities of religious organizations (except for the cases of violating laws) is included in the Law on Religious Organizations. Separation of religious organizations from the public rights sector presently is not being implemented. In state schools there are religious instruction lessons, religious organizations carry out religious activity in medical institutions and prisons, a service of chaplains has been established whose activity is funded from the state budget. Equality of the forms of activity of religious organizations is not guaranteed, since there exists a multi-stage registration system. A state function of performing marriage ceremonies is delegated to religious organizations. Thus, state functions are delegated to religious organizations. Besides the religious organizations are offered direct and indirect financial support which manifests in allotting tax relief as well as allocating direct grants from the state budget. The model having been established in the Republic of Latvia is a model of cooperation between the State and religious organizations. In the Constitution no state religion is provided but also no segregation of the State and religious organizations is realized. The State acknowledges the autonomy of religious organizations, however, the religious organizations receive financial support, definite functions are delegated to them, and religious organizations are operating in the public sector. Satversme lacks provisions that would truly provide that no state church exists in Latvia, but at the same time definite procedures and operations are being delegated to the church as stated by the law. The idea of amending the Satversme of the Republic of Latvia ought to be considered that would contain the provision about the model of cooperation between the State and religious organizations being realized in practice.
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Jordan, Carol Walker. "Order and Ardor: The Revival Spirituality of Oliver Hart and the Regular Baptists in Eighteenth-Century South Carolina." Southeastern Librarian 67, no. 1 (May 9, 2019). http://dx.doi.org/10.62915/0038-3686.1796.
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Bancks, Michael P., Meng-Yun Lin, Alain G. Bertoni, Wendell Futrell, Zhixiu Liu, Brian Ostasiewski, Brian J. Wells, and Amresh Hanchate. "Abstract MP11: Impact Of Severe Acute Respiratory Syndrome Coronavirus 2 (sars-cov-2) Pandemic On Diabetes Care Among A North Carolina Patient Population." Circulation 145, Suppl_1 (March 2022). http://dx.doi.org/10.1161/circ.145.suppl_1.mp11.
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Introduction: We assessed whether the coronavirus disease 2019 (COVID-19) pandemic was associated with within-individual delays in diabetes care processes of glycated hemoglobin (HbA1c) testing, retinal exam, and nephropathy evaluation among patients receiving regular care with Wake Forest Baptist Health (WFBH), overall and stratified by clinical factors, race and ethnicity, and socioeconomic status. Methods: We used electronic health record data for 25,323 WFBH adult patients with diabetes (96% type 2; 53% women; mean age ± SD: 63±13 years). We used Current Procedural Terminology codes to identify each diabetes care process occurring between 3/1/2018 and 2/28/2021. Delayed care between serial assessments was defined as a duration of >6 months for HbA1c testing and >12 months for retinal exam and nephropathy evaluation. We used individual-level fixed effects regression to estimate within-person change in outcomes before and after the start of the COVID-19 pandemic (3/1/2020), overall and among subgroups. Results: During the pandemic, there was a 12.7 to 20.6 percentage point increase in the incidence of delayed diabetes care ( Table ). We did not observe clinically meaningful differences in delayed care for any of the diabetes care procedures during the pandemic across socio-demographic subgroups. However, individuals with the highest HbA1c and greatest burden of comorbidities, respectively, had the greatest increase in the incidence of a delayed HbA1c test during the pandemic. Conclusions: The COVID-19 pandemic was associated with an increase in within-individual delays in HbA1c testing, retinal exams, and nephropathy evaluations. Delays were greatest for individuals with the most severe disease and may portend an increase in diabetes complications.
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De Araujo, Valter Shuenquener, and GABRIEL DE ANDRADE CAVALCANTI. "O Poder de Polícia nas Sociedades de Vigilância: história, limites e perspectivas." REVISTA QUAESTIO IURIS 16, no. 2 (December 12, 2023). http://dx.doi.org/10.12957/rqi.2023.64654.
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