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The stem cell hypothesis suggests that there is a small group of malignant cells, the cancer stem cells, that initiate the development of tumors, encourage its growth, and may even be the cause of metastases. Traditional treatments, such as chemotherapy and radiation, primarily target the tumor cells leaving the stem cells to potentially cause a recurrence. Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the immune cells are genetically modified to fight the tumor cells. Traditionally, the CAR T-cell therapy has been used to treat blood cancers and only recently has shown promising results against solid tumors. We create an ordinary differential equations model which allows for the infusion of trained CAR-T cells to specifically attack the cancer stem cells that are present in the solid tumor microenvironment. Additionally, we incorporate the influence of TGF-[Formula: see text] which inhibits the CAR-T cells and thus promotes the growth of the tumor. We verify the model by comparing it to available data and then examine combinations of CAR-T cell treatment targeting both non-stem and stem cancer cells and a treatment that reduces the effectiveness of TGF-[Formula: see text] to determine the scenarios that eliminate the tumor.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Conceitos Matemáticos , Modelos Biológicos , Neoplasias/terapia , Células-Tronco Neoplásicas , Fatores de Crescimento Transformadores/metabolismo , Microambiente TumoralRESUMO
In the quest for the identification of catalytic transformations to be used in chemical biology and medicinal chemistry, we identified iron(III) meso-tetraarylporphines as efficient catalysts for the reduction of aromatic azides to their amines. The reaction uses thiols as reducing agents and tolerates water, air, and other biological components. A caged fluorophore was employed to demonstrate that the reduction can be performed even in living mammalian cells. However, in vivo experiments in nematodes (Caenorhabditis elegans) and zebrafish (Danio rerio) revealed a limitation to this method: the metabolic reduction of aromatic azides.
Assuntos
Azidas/química , Compostos Férricos/química , Metaloporfirinas/química , Aminas/química , Animais , Caenorhabditis elegans , Catálise , Meio Ambiente , Células HeLa , Humanos , Oxirredução , Peixe-ZebraRESUMO
The need to focus on immunology education has never been greater. The coronavirus disease 2019 pandemic has revealed that a significant proportion of our society is vaccine hesitant. Some of this hesitancy may stem from a general lack of understanding of how the immune system and immunological interventions work. In addition, social media platforms undercut public health efforts by quickly propagating a multitude of misconceptions and erroneous information surrounding the science behind these interventions. The responsibility to be advocates for science is well recognized by immunology researchers, educators, and public health professionals, as evidenced by the rich body of resources developed to communicate science to the lay audience. Scientific jargon, however, can be a barrier to effective communication and can negatively impact learning and comprehension. The field of immunology is especially laden with discipline-specific terminology, which can hamper educators' efforts to convey key concepts to learners. Furthermore, a lack of consistency in accepted definitions can complicate students' conceptual understanding. Learning resources, including textbooks, published in print or available online, and exclusively digital resources, continue to serve as the primary sources of information for both educators and students. In this article, we describe a vast heterogeneity in learning resource glossary descriptions of two key conceptual terms: antigen and immunogen We provide a perspective on pedagogical strategies to address these critical terms. Using current knowledge, we recommend an approach to standardize the definitions of the terms antigen and immunogen within the immunology educator community.
Assuntos
COVID-19 , HumanosRESUMO
Although immunological research has become increasingly important in recent decades for understanding infectious and immune-mediated diseases, immunological pedagogy at the undergraduate level has lagged behind in reports of evidence-based scholarship. To address the need for a renewed emphasis on immunology education and to describe the current status of undergraduate education in immunology, an online survey of instructors with experience in teaching immunology was conducted. The survey investigated the effects of instructors' level of teaching experience, target student population, and course components on the emphasis given to certain immunology subtopics in their courses. Instructor teaching experience and current role in teaching influenced the proportion of time allotted to lab techniques, clinical topics, and evolutionary aspects, but type of institution (undergraduate and graduate degree-granting institutions) did not affect course content or emphasis on subtopics. Topics that received the greatest emphasis were the adaptive immune system, the innate immune system, host-pathogen interactions, and molecular mechanisms. Vaccines, hypersensitivity, autoimmunity, and essential immunology techniques were ranked slightly lower, while topics such as evolution, metabolism and antibody purification received the least emphasis. Inclusion of a lab component increased time given to lab-related and clinical topics but did not affect the perceived importance of various scientific competencies. These data describe current curricular practices of instructors who have experience teaching immunology and inform curricular priorities and course design frameworks for undergraduate immunology education.
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We propose a mathematical model to describe the interaction of cancer stem cells, tumor cells, and the immune system in order to better understand tumor growth in the presence of cancer stem cells. We consider the system in two scenarios: with no-treatment and with a chemotherapy treatment regimen. We develop a system of differential equations, fit the parameters to experimental data, and perform sensitivity and stability analysis. The model simulations show that the tumor cells grow as predicted with no-treatment and that with chemotherapy, which targets only the tumor cells, the cancer will eventually relapse. As chemotherapy does not target the cancer stem cells, we conclude that the tumor cells recover due to the presence of cancer stem cells.
Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Antineoplásicos/farmacologia , Linfócitos T CD8-Positivos/citologia , Calibragem , Esquema de Medicação , Fluoruracila/farmacologia , Humanos , Camundongos , Modelos Biológicos , Recidiva Local de Neoplasia , Neoplasias/patologia , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Nearly half of all undergraduates are enrolled at community colleges (CCs), including the majority of U.S. students who represent groups underserved in the sciences. Yet only a small minority of studies published in discipline-based education research journals address CC biology students, faculty, courses, or authors. This marked underrepresentation of CC biology education research (BER) limits the availability of evidence that could be used to increase CC student success in biology programs. To address this issue, a diverse group of stakeholders convened at the Building Capacity for Biology Education Research at Community Colleges meeting to discuss how to increase the prevalence of CC BER and foster participation of CC faculty as BER collaborators and authors. The group identified characteristics of CCs that make them excellent environments for studying biology teaching and learning, including student diversity and institutional cultures that prioritize teaching, learning, and assessment. The group also identified constraints likely to impede BER at CCs: limited time, resources, support, and incentives, as well as misalignment between doing research and CC faculty identities as teachers. The meeting culminated with proposing strategies for faculty, administrators, journal editors, scientific societies, and funding agencies to better support CC BER.
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Biologia/educação , Docentes , Pesquisa , Estudantes , Fortalecimento Institucional , Humanos , Instituições AcadêmicasRESUMO
Caenorhabditis elegans has become a useful model for studying innate immunity. ELT-2, which is homologous to human GATA-4, -5 and -6, is considered the primary GATA transcription factor controlling intestinal immunity in C. elegans. In this study, we characterize the timeline of intestinal distension in nematodes where ELT-2 and another intestinal GATA transcription factor, ELT-7, are abrogated by RNAi using two different models: colonization and toxin-based infections by Pseudomonas aeruginosa. We show that both ELT-2 and ELT-7 are important for survival of C. elegans exposed to P. aeruginosa. Intestinal distension is accelerated in elt-2 RNAi nematodes, and is observed in colonization but not toxin-based Pseudomonas infection. Upon onset of intestinal distension, nematodes die within 24 h, regardless of experimental treatment. These data provide new insight into the role of ELT-2 and ELT-7 in protecting C. elegans against P. aeruginosa infection.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/imunologia , Caenorhabditis elegans/microbiologia , Fatores de Transcrição GATA/metabolismo , Pseudomonas aeruginosa , Animais , Intestinos/microbiologia , Interferência de RNARESUMO
Despite numerous reports that active learning increases student understanding, many barriers still exist that prevent faculty from shedding the traditional passive lecture and adopting active learning strategies in the classroom. This study looks at the use of role play as an active learning technique to convey new material, or as reinforcement to traditional lecture. A pre- and post-test survey was utilized to determine student learning gains, along with an anonymous survey to determine student attitudes about role play. Student learning gains are similar regardless of class size, role-playing participation or learning style, and reflect an increase in lower order cognition. Attitudes and learning gains indicate role play is preferable as a reinforcement technique, although the order does not matter if both lecture and role play are utilized to convey information. These data provide insight into the best practices of role-playing implementation in concert with traditional lecture format.