Potential Epigenetic Mechanism(s) Associated With the Persistence of Psychoneurological Symptoms in Women Receiving Chemotherapy for Breast Cancer

Due to recent treatment advances, there have been improvements in the proportion of women surviving a diagnosis of breast cancer (BC). However, many of these survivors report persistent adverse side effects following treatment, such as cognitive dysfunction, depressive symptoms, anxiety, fatigue, sleep disturbances, and pain. Investigators have examined circulating levels of inflammatory markers, particularly serum cytokines, for a potential causal relationship to the development/persistence of these psychoneurological symptoms (PNS). While inflammatory activation, resulting from perceived stress or other factors, may directly contribute to the development of PNS, we offer an alternative hypothesis, suggesting that these symptoms are an early step in a cascade of biological changes leading to epigenetic alterations at the level of deoxyribonucleic acid (DNA) methylation, histone modifications, and/or chromatin structure/chromosomal instability. Given that epigenetic patterns have plasticity, if this conjectured relationship between epigenomic/acquired genomic alterations and the development/persistence of PNS is confirmed, it could provide foundational knowledge for future research leading to the recognition of predictive markers and/or treatments to alleviate PNS in women with BC. In this article, we discuss an evolving theory of the biological basis of PNS, integrating knowledge related to inflammation and DNA repair in the context of genetic and epigenetic science to expand the paradigm for understanding symptom acquisition/persistence following chemotherapy.

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Epigenetic alterations in endocrine-related cancer

Endocrine Related Cancer ◽

10.1530/erc-13-0070 ◽

2014 ◽

Vol 21 (4) ◽

pp. R319-R330 ◽

Cited By ~ 14

Author(s):

Sandra Rodríguez-Rodero ◽

Elías Delgado-Álvarez ◽

Agustín F Fernández ◽

Juan L Fernández-Morera ◽

Edelmiro Menéndez-Torre ◽

...

Keyword(s):

Endocrine System ◽

Future Research ◽

Epigenetic Alterations ◽

Post Translational Modification ◽

Sequencing Technologies ◽

Genome Wide ◽

Cancer Tumor ◽

Cancer Types ◽

Tumor Types ◽

Epigenetic Patterns

Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

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Learning from and Leveraging Multi-Level Changes in Responses to the COVID 19 Pandemic to Facilitate Breast Cancer Prevention Efforts

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18136999 ◽

2021 ◽

Vol 18 (13) ◽

pp. 6999

Author(s):

Deborah J. Bowen ◽

Kelly E. Rentscher ◽

Amy Wu ◽

Gwen Darien ◽

Helen Ghirmai Haile ◽

...

Keyword(s):

Breast Cancer ◽

Health Care ◽

Cancer Prevention ◽

Care Delivery ◽

Breast Cancer Prevention ◽

Health Care Use ◽

Economic Life ◽

Future Research ◽

Multi Level ◽

And Shifts

The coronavirus pandemic (COVID-19) has had multilevel effects on non-COVID-19 health and health care, including deferral of routine cancer prevention and screening and delays in surgical and other procedures. Health and health care use has also been affected by pandemic-related loss of employer-based health insurance, food and housing disruptions, and heightened stress, sleep disruptions and social isolation. These disruptions are projected to contribute to excess non-COVID-19 deaths over the coming decades. At the same time municipalities, health systems and individuals are making changes in response to the pandemic, including modifications in the environmental to promote health, implementation of telehealth platforms, and shifts towards greater self-care and using remote platforms to maintain social connections. We used a multi-level biopsychosocial model to examine the available literature on the relationship between COVID-19-related changes and breast cancer prevention to identify current gaps in knowledge and identify potential opportunities for future research. We found that COVID-19 has impacted several aspects of social and economic life, through a variety of mechanisms, including unemployment, changes in health care delivery, changes in eating and activity, and changes in mental health. Some of these changes should be reduced, while others should be explored and enhanced.

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Understanding low chemoprevention uptake by women at high risk of breast cancer: findings from a qualitative inductive study of women’s risk-reduction experiences

BMC Women s Health ◽

10.1186/s12905-021-01279-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tasleem J. Padamsee ◽

Megan Hils ◽

Anna Muraveva

Keyword(s):

Breast Cancer ◽

African American ◽

High Risk ◽

Risk Reduction ◽

White Women ◽

Future Research ◽

Structured Interviews ◽

Critical Gap ◽

High Risk Women ◽

Parent Project

Abstract Background Chemoprevention is one of several methods that have been developed to help high-risk women reduce their risk of breast cancer. Reasons for the low uptake of chemoprevention are poorly understood. This paper seeks a deeper understanding of this phenomenon by drawing on women’s own narratives about their awareness of chemoprevention and their risk-related experiences. Methods This research is based on a parent project that included fifty in-depth, semi-structured interviews with a purposive sample of African American and White women at elevated risk of breast cancer. This specific study draws on the forty-seven interviews conducted with women at high or severe risk of breast cancer, all of whom are eligible to use chemoprevention for breast cancer risk-reduction. Interviews were analyzed using grounded theory methods. Results Forty-five percent of participants, and only 21% of African American participants, were aware of chemoprevention options. Women who had seen specialists were more likely to be aware, particularly if they had ongoing specialist access. Aware and unaware women relied on different types of sources for prevention-related information. Those whose main source of information was a healthcare provider were more likely to know about chemoprevention. Aware women used more nuanced information gathering strategies and worried more about cancer. Women simultaneously considered all risk-reduction options they knew about. Those who knew about chemoprevention but were reluctant to use it felt this way for multiple reasons, having to do with potential side effects, perceived extreme-ness of the intervention, similarity to chemotherapy, unknown information about chemoprevention, and reluctance to take medications in general. Conclusions Lack of chemoprevention awareness is a critical gap in women’s ability to make health-protective choices. Future research in this field must consider complexities in both women’s perspectives on chemoprevention and the reasons they are reluctant to use it.

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Impact of Shift Work and Long Working Hours on Worker Cognitive Functions: Current Evidence and Future Research Needs

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18126540 ◽

2021 ◽

Vol 18 (12) ◽

pp. 6540

Author(s):

Veruscka Leso ◽

Luca Fontana ◽

Angela Caturano ◽

Ilaria Vetrani ◽

Mauro Fedele ◽

...

Keyword(s):

Circadian Rhythm ◽

Cognitive Impairment ◽

Sleep Disturbances ◽

Working Hours ◽

Night Work ◽

Current Evidence ◽

Future Research ◽

Negative Effects ◽

Long Working Hours ◽

Main Determinants

Particular working conditions and/or organization of working time may cause important sleep disturbances that have been proposed to be predictive of cognitive decline. In this regard, circadian rhythm misalignment induced by exposure to night work or long working hours would be responsible for cognitive impairment. Nevertheless, evidence supporting this correlation is limited and several issues still need to be elucidated. In this regard, we conducted a systematic review to evaluate the association between shift/night work and cognitive impairment and address its main determinants. Information provided by the reviewed studies suggested that night work might have serious immediate negative effects especially on cognitive domains related to attention, memory and response inhibition. Furthermore, cognitive performance would progressively worsen over consecutive night shifts or following exposure to very long work shifts. Otherwise, conflicting results emerged regarding the possible etiological role that night work chronic exposure would have on cognitive impairment. Therefore, circadian rhythm desynchronization, lack of sleep and fatigue resulting from night work may negatively impact worker’s cognitive efficiency. However, in light of the considerable methodological variability of the reviewed studies, we proposed to develop a standardized research and evaluation strategy in order to obtain a better and comprehensive understanding of this topic.

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Sub-Ethnicity and Survivorship Experience: Asian American Breast Cancer Survivors

Western Journal of Nursing Research ◽

10.1177/01939459211031990 ◽

2021 ◽

pp. 019394592110319

Author(s):

Wonshik Chee ◽

Eun-Ok Im

Keyword(s):

Breast Cancer ◽

Cancer Survivors ◽

Asian American ◽

Breast Cancer Survivors ◽

Short Form ◽

Secondary Analysis ◽

Future Research ◽

Japanese American ◽

Personal Resource ◽

Cancer Data

The purpose of the study was to explore the associations of sub-ethnicity to the survivorship experience of Asian American breast cancer survivors and identify the multiple factors that influenced their survivorship experience. This was a secondary analysis of the data among 94 Asian American breast cancer survivors from a larger ongoing study. Instruments included: questions on background characteristics, the perceived isolation scale, the Personal Resource Questionnaire, the Memorial Symptom Assessment Scale-Short Form, and the Functional Assessment of Cancer Therapy-Breast Cancer. Data were analyzed using hierarchical logistic and multiple regression analyses. After controlling for other factors, being a Japanese American (ref. = being a Chinese American) was significantly associated with pain scores (odds ratio [OR] = −0.32, p < .01), symptom distress scores ( β = −0.27, p < .01), and the quality of life scores ( β = 0.22, p = .03). Sub-ethnic variations in cultural attitudes, values, and beliefs need to be considered in future research/practice with Asian American breast cancer survivors.

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Distinct Ring1b complexes defined by DEAD-box helicases and EMT transcription factors synergistically enhance E-cadherin silencing in breast cancer

Cell Death and Disease ◽

10.1038/s41419-021-03491-4 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Yawei Wang ◽

Yingying Sun ◽

Chao Shang ◽

Lili Chen ◽

Hongyu Chen ◽

...

Keyword(s):

Breast Cancer ◽

Transcription Factors ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Epigenetic Mechanism ◽

Regulation Mechanism ◽

Rna Helicases ◽

Mesenchymal Transition ◽

Dead Box ◽

E Cadherin

AbstractRing1b is a core subunit of polycomb repressive complex 1 (PRC1) and is essential in several high-risk cancers. However, the epigenetic mechanism of Ring1b underlying breast cancer malignancy is poorly understood. In this study, we showed increased expression of Ring1b promoted metastasis by weakening cell–cell adhesions of breast cancer cells. We confirmed that Ring1b could downregulate E-cadherin and contributed to an epigenetic rewiring via PRC1-dependent function by forming distinct complexes with DEAD-box RNA helicases (DDXs) or epithelial-mesenchymal transition transcription factors (EMT TFs) on site-specific loci of E-cadherin promoter. DDXs-Ring1b complexes moderately inhibited E-cadherin, which resulted in an early hybrid EMT state of epithelial cells, and EMT TFs-Ring1b complexes cooperated with DDXs-Ring1b complexes to further repress E-cadherin in mesenchymal-like cancer cells. Clinically, high expression of Ring1b with DDXs or EMT TFs predicted low levels of E-cadherin, metastatic behavior, and poor prognosis. These findings provide an epigenetic regulation mechanism of Ring1b complexes in E-cadherin expression. Ring1b complexes may be potential therapeutic targets and biomarkers for diagnosis and prognosis in invasion breast cancer.

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Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Molecules ◽

10.3390/molecules26144330 ◽

2021 ◽

Vol 26 (14) ◽

pp. 4330

Author(s):

Jean-François Mallet ◽

Roghayeh Shahbazi ◽

Nawal Alsadi ◽

Chantal Matar

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Mirna Expression ◽

Epigenetic Mechanism ◽

Breast Cancer Cell Lines ◽

Relative Expression ◽

Target Proteins ◽

Pathological Characteristics

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.

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A Systematic Review of Sleep and Circadian Rhythms in Children with Attention Deficit Hyperactivity Disorder

Journal of Attention Disorders ◽

10.1177/1087054720978556 ◽

2021 ◽

pp. 108705472097855

Author(s):

Upasana Bondopadhyay ◽

Unai Diaz-Orueta ◽

Andrew N. Coogan

Keyword(s):

Systematic Review ◽

Circadian Rhythms ◽

Sleep Disturbances ◽

Behavioral Outcomes ◽

Future Research ◽

Narrative Synthesis ◽

Adhd Symptoms ◽

Children With Adhd ◽

Hyperactivity Disorder ◽

Form Part

Objective: Children and adults with ADHD often report sleep disturbances that may form part of the etiology and/or symptomatology of ADHD. We review the evidence for sleep changes in children with ADHD. Methods: Systematic review with narrative synthesis assessing sleep and circadian function in children aged 5 to 13 years old with a diagnosis of ADHD. Results: 148 studies were included for review, incorporating data from 42,353 children. We found that sleep disturbances in ADHD are common and that they may worsen behavioral outcomes; moreover, sleep interventions may improve ADHD symptoms, and pharmacotherapy for ADHD may impact sleep. Conclusion: Sleep disturbance may represent a clinically important feature of ADHD in children, which might be therapeutically targeted in a useful way. There are a number of important gaps in the literature. We set out a manifesto for future research in the area of sleep, circadian rhythms, and ADHD.

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Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

Antioxidants ◽

10.3390/antiox10081232 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1232

Author(s):

Sadaf Harandi-Zadeh ◽

Cayla Boycott ◽

Megan Beetch ◽

Tony Yang ◽

Benjamin J. E. Martin ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dna Methyltransferase ◽

Epigenetic Marks ◽

Chip Sequencing ◽

Dietary Polyphenols ◽

A Genome ◽

Epigenetic Patterns

Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B (DNMT3B) as vital players in PTS-mediated suppression of candidate oncogenes and suggested a role of enhancers as target regions. In the present study, we assess a genome-wide impact of PTS on epigenetic marks at enhancers in highly invasive MCF10CA1a breast cancer cells. Following chromatin immunoprecipitation (ChIP)-sequencing in MCF10CA1a cells treated with 7 μM PTS for 9 days, we discovered that PTS leads to increased binding of DNMT3B at enhancers of 77 genes, and 17 of those genes display an overlapping decrease in the occupancy of trimethylation at lysine 36 of histone 3 (H3K36me3), a mark of active enhancers. We selected two genes, PITPNC1 and LINC00910, and found that their enhancers are hypermethylated in response to PTS. These changes coincided with the downregulation of gene expression. Of importance, we showed that 6 out of 17 target enhancers, including PITPNC1 and LINC00910, are bound by an oncogenic transcription factor OCT1 in MCF10CA1a cells. Indeed, the six enhancers corresponded to genes with established or putative cancer-driving functions. PTS led to a decrease in OCT1 binding at those enhancers, and OCT1 depletion resulted in PITPNC1 and LINC00910 downregulation, further demonstrating a role for OCT1 in transcriptional regulation. Our findings provide novel evidence for the epigenetic regulation of enhancer regions by dietary polyphenols in breast cancer cells.

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