scholarly journals Epigenetic mechanisms driving tumor supportive microenvironment differentiation and function: a role in cancer therapy?

Epigenomics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 157-169 ◽  
Author(s):  
Marvin Sylvestre ◽  
Karin Tarte ◽  
David Roulois
Keyword(s):  
Stromal Cell ◽  
Somatic Mutations ◽  
Tumor Development ◽  
Cell Subset ◽  
Heterogeneous Population ◽  
Cancer Associated Fibroblasts ◽  
Epigenetic Mechanisms ◽  
Immunosuppressive Microenvironment ◽  
And Function ◽  
The Impact

The tumor microenvironment (TME) plays a central role in tumor development and drug resistance. Within TME, the stromal cell subset, called cancer-associated fibroblasts, is a heterogeneous population originating from poorly characterized precursors. Since cancer-associated fibroblasts do not acquire somatic mutations, other mechanisms like epigenetic regulation, could be involved in the development of these cells and in the acquisition of tumor supportive phenotypes. Moreover, such epigenetic modulations have been correlated to the emergence of an immunosuppressive microenvironment facilitating tumor evasion. These findings underline the need to deepen our knowledge on epigenetic mechanisms driving TME development and function, and to understand the impact of epigenetic drugs that could be used in future to target both tumor cells and their TME.

scholarly journals Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2602
Author(s):  
Emilie Viennois ◽  
Benoit Chassaing
Keyword(s):  
Intestinal Inflammation ◽  
Tumor Development ◽  
Low Grade ◽  
Gastrointestinal Cancers ◽  
Cancer Initiation ◽  
And Function ◽  
The Impact ◽  
Chronic Intestinal Inflammation ◽  
Low Grade Inflammation ◽  
Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

scholarly journals TFEB is a master regulator of tumor-associated macrophages in breast cancer

2020 ◽  
Vol 8 (1) ◽  
pp. e000543 ◽  
Author(s):  
Yong Li ◽  
Johnie Hodge ◽  
Qing Liu ◽  
Junfeng Wang ◽  
Yuzhen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Growth ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Breast Tumor ◽  
Tumor Development ◽  
Tumor Associated Macrophages ◽  
And Function ◽  
The Impact

BackgroundTumor-associated macrophages (TAMs) play key roles in the development of many malignant solid tumors including breast cancer. They are educated in the tumor microenvironment (TME) to promote tumor growth, metastasis, and therapy resistance. However, the phenotype of TAMs is elusive and how to regulate them for therapeutic purpose remains unclear; therefore, TAM-targeting therapies have not yet achieved clinical success. The purposes of this study were to examine the role of transcription factor EB (TFEB) in regulating TAM gene expression and function and to determine if TFEB activation can halt breast tumor development.MethodsMicroarrays were used to analyze the gene expression profile of macrophages (MΦs) in the context of breast cancer and to examine the impact of TFEB overexpression. Cell culture studies were performed to define the mechanisms by which TFEB affects MΦ gene expression and function. Mouse studies were carried out to investigate the impact of MΦ TFEB deficiency or activation on breast tumor growth. Human cancer genome data were analyzed to reveal the prognostic value of TFEB and its regulated genes.ResultsTAM-mimic MΦs display a unique gene expression profile, including significant reduction in TFEB expression. TFEB overexpression favorably modulates TAM gene expression through multiple signaling pathways. Specifically, TFEB upregulates suppressor of cytokine signaling 3 (SOCS3) and peroxisome proliferator-activated receptor γ (PPARγ) expression and autophagy/lysosome activities, inhibits NLRP3 (NLR Family Pyrin Domain Containing 3) inflammasome and hypoxia-inducible factor (HIF)-1α mediated hypoxia response, and thereby suppresses an array of effector molecules in TAMs including arginase 1, interleukin (IL)-10, IL-1β, IL-6 and prostaglandin E2. MΦ-specific TFEB deficiency promotes, while activation of TFEB using the natural disaccharide trehalose halts, breast tumor development by modulating TAMs. Analysis of human patient genome database reveals that expression levels of TFEB, SOCS3 and PPARγ are positive prognostic markers, while HIF-1α is a negative prognostic marker of breast cancer.ConclusionsOur study identifies TFEB as a master regulator of TAMs in breast cancer. TFEB controls TAM gene expression and function through multiple autophagy/lysosome-dependent and independent pathways. Therefore, pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer by favorably modulating TAM function and the TME.

scholarly journals Assessment of Lymph Node Stromal Cells as an Underlying Factor in Age-Related Immune Impairment

2019 ◽  
Vol 74 (11) ◽  
pp. 1734-1743 ◽  
Author(s):  
April R Masters ◽  
Alexxus Hall ◽  
Jenna M Bartley ◽  
Spencer R Keilich ◽  
Erica C Lorenzo ◽  
...  
Keyword(s):  
T Cells ◽  
Steady State ◽  
Immune Responses ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Influenza Infection ◽  
Cell Subset ◽  
The Elderly ◽  
Age Related ◽  
The Impact

Abstract Aging negatively impacts immunity, resulting in inefficient responses to vaccinations and infections. Fibroblastic reticular cells (FRCs) are the major stromal cell subset in lymph nodes (LNs) and play an intricate role in the orchestration and control of adaptive immune responses. Although stromal cells have a major impact on immune responses, the impact of aging on LN stromal cells remains unclear. Quantitative analysis of LN stromal cells by flow cytometry revealed that there are no significant differences in the number of stromal cells in young and aged LN at steady state but after influenza infection aged FRCs have delayed expansion as a result of reduced proliferation. Aged LNs also produce reduced levels of homeostatic chemokines, which correlates with reduced homing of naive T cells. Image analysis reveals that young and aged T-cell zone FRCs have similar morphology at steady state and after infection. Furthermore, aged FRCs did not appear to be a contributing factor in the reduced proliferation of young T cells transferred into aged LNs after influenza infection. These results demonstrate that aging alters LN stromal cell response to challenge and these age-related changes may be an underlying contributor to impaired immune responses in the elderly people.

scholarly journals Modeling Somatic Mutations Associated With Neurodevelopmental Disorders in Human Brain Organoids

2022 ◽  
Vol 14 ◽  
Author(s):  
Bipan K. Deb ◽  
Helen S. Bateup
Keyword(s):  
Human Brain ◽  
Brain Development ◽  
Neurodevelopmental Disorders ◽  
Somatic Mutations ◽  
De Novo ◽  
Intractable Epilepsy ◽  
Model Systems ◽  
Loss Of Function ◽  
And Function ◽  
The Impact

Neurodevelopmental disorders (NDDs) are a collection of diseases with early life onset that often present with developmental delay, cognitive deficits, and behavioral conditions. In some cases, severe outcomes such as brain malformations and intractable epilepsy can occur. The mutations underlying NDDs may be inherited or de novo, can be gain- or loss-of-function, and can affect one or more genes. Recent evidence indicates that brain somatic mutations contribute to several NDDs, in particular malformations of cortical development. While advances in sequencing technologies have enabled the detection of these somatic mutations, the mechanisms by which they alter brain development and function are not well understood due to limited model systems that recapitulate these events. Human brain organoids have emerged as powerful models to study the early developmental events of the human brain. Brain organoids capture the developmental progression of the human brain and contain human-enriched progenitor cell types. Advances in human stem cell and genome engineering provide an opportunity to model NDD-associated somatic mutations in brain organoids. These organoids can be tracked throughout development to understand the impact of somatic mutations on early human brain development and function. In this review, we discuss recent evidence that somatic mutations occur in the developing human brain, that they can lead to NDDs, and discuss how they could be modeled using human brain organoids.

scholarly journals The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2912 ◽  
Author(s):  
Laurence Blavier ◽  
Ren-Ming Yang ◽  
Yves A. DeClerck
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Complex Nature ◽  
Cancer Associated Fibroblasts ◽  
Immunosuppressive Activity ◽  
And Function ◽  
The Impact ◽  
Initial Focus

The contribution of the tumor microenvironment (TME) to cancer progression has been well recognized in recent decades. As cancer therapeutic strategies are increasingly precise and include immunotherapies, knowledge of the nature and function of the TME in a tumor becomes essential. Our understanding of the TME in neuroblastoma (NB), the second most common solid tumor in children, has significantly progressed from an initial focus on its Schwannian component to a better awareness of its complex nature, which includes not only immune but also non-immune cells such as cancer-associated fibroblasts (CAFs), the contribution of which to inflammation and interaction with tumor-associated macrophages (TAMs) is now recognized. Recent studies on the TME landscape of NB tumors also suggest significant differences between MYCN-amplified (MYCN-A) and non-amplified (MYCN-NA) tumors, in their content in stromal and inflammatory cells and their immunosuppressive activity. Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Investigating Burnt Mounds in Clydesdale during Motorway Construction

1998 ◽  
Vol 21 (1) ◽  
pp. 1-28
Author(s):  
John A Atkinson ◽  
Camilla Dickson ◽  
Jane Downes ◽  
Paul Robins ◽  
David Sanderson
Keyword(s):  
Bronze Age ◽  
Research Strategy ◽  
Archaeological Evidence ◽  
Radiocarbon Dates ◽  
Short Account ◽  
And Function ◽  
The Impact ◽  
The Bronze Age

Summary Two small burnt mounds were excavated as part of the programme to mitigate the impact of motorway construction in the Crawford area. The excavations followed a research strategy designed to address questions of date and function. This paper surveys the various competing theories about burnt mounds and how the archaeological evidence was evaluated against those theories. Both sites produced radiocarbon dates from the Bronze Age and evidence to suggest that they were cooking places. In addition, a short account is presented of two further burnt mounds discovered during the construction of the motorway in Annandale.

768 THE ORIGIN AND FUNCTION OF CANCER-ASSOCIATED FIBROBLASTS IN COLORECTAL CARCINOGENESIS

2020 ◽  
Vol 158 (6) ◽  
pp. S-160
Author(s):  
Hiroki Kobayashi ◽  
Krystyna Gieniec ◽  
Tamsin Lannagan ◽  
Tongtong Wang ◽  
Samuel Asfaha ◽  
...  
Keyword(s):  
Colorectal Carcinogenesis ◽  
Cancer Associated Fibroblasts ◽  
And Function

Understanding Motivating Operations and the Impact on the Function of Behavior

2020 ◽  
Vol 56 (2) ◽  
pp. 119-122
Author(s):  
Doris Adams Hill ◽  
Theoni Mantzoros ◽  
Jonté C. Taylor
Keyword(s):  
Behavioral Interventions ◽  
Special Educators ◽  
Motivating Operations ◽  
Behavior Intervention Plans ◽  
Education Professionals ◽  
Functional Behavior ◽  
Special Education Professionals ◽  
And Function ◽  
And Behavior ◽  
The Impact

Special educators are often considered the experts in their school when it comes to developing functional behavior assessments (FBA) and behavior intervention plans (BIP), yet rarely are they trained much beyond basic antecedents, behaviors, and consequences (ABC). This column discusses concepts that will expand special education professionals’ knowledge to make better decisions regarding interventions for the students they serve. Specifically, the focus is on motivating operations (MO) and function-based interventions and the implications of these on behavior. Knowledge of the concept of MOs can enhance a teacher’s ability to provide evidence-based interventions and more fully developed behavioral interventions for students in their purview.

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