scholarly journals The chromatin remodeler SMARCD3 regulates cell cycle progression and its expression predicts survival outcome in ER+ breast cancer

2019 ◽  
Author(s):  
Romain Tropée ◽  
Bárbara de la Peña Avalos ◽  
Madeline Gough ◽  
Cameron Snell ◽  
Pascal H.G. Duijf ◽  
...  

AbstractChromatin remodeling plays an essential role in regulating transcriptional networks and timing of gene expression. Chromatin remodelers such as SWItch/Sucrose Non-Fermentable (SWI/SNF) harbor many protein components, with the catalytic subunit providing ATPase activity to displace histones along or from the DNA molecules, and associated subunits ensuring tissue specificity and transcriptional or co-transcriptional activities. Mutations in several of the SWI/SNF subunits have been linked to cancer. Here, we describe how SMARCD3/Baf60c expression is associated with hormone positive (ER+) breast cancer. The level SMARCD3, as detected by immunohistochemistry in breast cancer patient samples, is correlated with differential long-term disease-free survival. In contrast, the expression level of SMARCD1/Baf60a and SMARCD2/Baf60b, which are mutually exclusive within the SWI/SNF complex and have a partially redundant function, lacks predictive value in breast cancer patient samples. Lower proliferation rates are observed in SMARCD3 depleted cells, which reflects a failure to fully progress through G2/M, and an increase in endoreplication. In the absence of SMARCD3, p21 accumulates in cells but does not halt the cell cycle, and DNA damage accumulates and remains unrepaired. Taken together, our data begin to explain why ER+ breast cancer patients with low SMARCD3 expressing tumors exhibit reduced survival rates compared to patients expressing normal or higher levels of SMARCD3. SMARCD3 might act as a tumor suppressor role through regulation of cell cycle checkpoints and could be a reliable and specific breast cancer prognostic biomarker.SignificanceMutations in chromatin remodelers are a leading cause of cancer. Estrogen Receptor positive (ER+) breast cancers represent approximately 80% of all cases diagnosed. Although these tumors can be treated with hormone therapy, most breast cancer fatalities occur in ER+ breast cancer patients, due to metastasis. Low expression of SMARCD3 in ER+ cancer is associated with diminished survival rates. As such, SMARCD3 could be used as a predictive biomarker for survival. In addition, we have identified a role for SMARCD3 in the cell cycle, which could at least partially explain its protective role in breast cancer. While catalytic subunits are often viewed as the major components in chromatin remodeling function, we show here new evidence that mutations or silencing of SMARCD3 may also contribute to genomic instability and thus development of breast cancer.

2021 ◽  
Vol 9 (E) ◽  
pp. 624-628
Author(s):  
Azriful Azriful ◽  
Fatmawaty Mallapiang ◽  
Yessy Kurniati

BACKGROUND: Social determinants have an important role in the survival of breast cancer patients. AIM: This article aims to reviews the social determinants that affect the survival of breast cancer patient. METHODS: We searched PubMed and Google Scholar for identifying studies related to this review using free-text terms and Medical Subject Headings terms. Both experimental and observational studies on social determinants of breast cancer patient survival which were published in the English language have been included in this review except expert opinions, commentaries, editorials, and review articles. Ten studies were eligible to be included in review. RESULTS: Social health determinants that play a role in the survival of breast cancer patients are education level, place of residence, socioeconomic status, social environment, racial discrimination, and access to health services. CONCLUSION: Social determinants have an influence on the survival of breast cancer patients, so it is important to pay attention to these factors.


2016 ◽  
Vol 17 (5) ◽  
pp. 531-543
Author(s):  
Yuko K Abbott

Summary This study was conducted to understand the impact of oncology social work office location on breast cancer patients’ access and utilization of social work services. It also explored the current status of oncology social work offices and the perceptions among Association of Oncology Social Work Listserv members. The frequency and types of interventions and referral time were determined retrospectively. Association of Oncology Social Work Listserv members were surveyed. Findings From 461 new breast cancer patient charts, 52 were referred to social work during study period. Face-to-face interventions decreased by 0.8 contact ( p = .0221) and telephone interventions increased by 1.8 contacts ( p = .0293) after social work office was relocated away from clinical area. Referral time to social work services decreased unexpectedly by 14.5 days ( p = .076) after office relocation. Association of Oncology Social Work Listserv survey results identify an office location as possible barrier, though most respondents have a private office in clinical area, accessible to patients. Survey finding is limited due to low response rate. Applications There are many challenges to ensuring timey and effective delivery of social work services to breast cancer patients. Social Ecological framework is used to understand the impacts of office location on access to social work services. Study results suggest that office relocation has had mix impacts on patients. Raising awareness of social worker services among patients early in cancer trajectory is needed for patient empowerment and to ensure access to social work services. Further research is needed to understand barriers, identify effective strategies in order to guide and improve clinical practice.


2019 ◽  
Vol 10 (2) ◽  
pp. 298
Author(s):  
Ni Made Merlin ◽  
Anggorowati Anggorowati ◽  
Chandra Bagus Ropyanto ◽  
Antonius Rino Vanchapo

<p>Breast cancer patients experience low self-acceptance and some of the experiencing psychological problems but not a lot of research to increasing self-acceptance. Additional intervention is needed to improve the effectiveness to increase self-acceptance. Technique relaxation is especially related because easy and quick to learn, it involves no risk, does not need use or purchased equipment and can be used on its own and immediately to tiredness and ill patients. This paper offers a literature review assessing the implications of previous studies order to create evidence-based decisions about the possibility to use of relaxation techniques with adult breast cancer patient for low self-acceptance. The Science Direct, EBSCOhost, Pubmed, DOAJ, Google Scholar database were searched in 2017 in orders to replied two questions: are relaxation technique effective to increase self-acceptance in breast cancer patients, and implications the previous investigation to future research concerning increase self-acceptance in breast cancer patients? Four articles included in the literature review. The relaxation technique for breast cancer patients with low self-acceptance is statically significant, and good evidence-based to practice. Some use of relaxation techniques in this study needs clarification as to whether it can be used directly or need to learn. Procedures in the collection of data in the articles also need to be assessed. In this literature review explain 4 relaxation technique to use for increasing self-acceptance in breast cancer, there are self-forgiveness, meditation, tai-chi, reflection, prayer, mindfulness. This literature review can be used as the basis for the decision to use relaxation techniques for increasing self-acceptance in the breast cancer patient.</p>


Author(s):  
Yudai Kaneda ◽  
Akihiko Ozaki ◽  
Masahiro Wada ◽  
Tomohiro Kurokawa ◽  
Toyoaki Sawano ◽  
...  

Little is known on how disasters interact in their impacts on patient care. We experienced a breast cancer patient whose initial presentation was delayed for two years due to the COVID-19 pandemic and Typhoon Hagibis. Increasing awareness is needed on the combined impacts of disasters on breast cancer management.


2006 ◽  
Vol 13 (4) ◽  
pp. 121-123
Author(s):  
G. Fan ◽  
E. Sinclair ◽  
M. Christakis ◽  
L. Erhlich ◽  
J. Zubovits ◽  
...  

Post-mastectomy radiotherapy has been demonstrated to improve locoregional control in breast cancer patients. We report a case involving a 44-year-old breast cancer patient who presented with a solitary bone metastasis in the area beneath the shoulder shield, likely from a coincidental recurrence.


2017 ◽  
Vol 63 (2) ◽  
pp. 316-319 ◽  
Author(s):  
Valentina Chulkova ◽  
Tatyana Semiglazova ◽  
Margarita Vagaytseva ◽  
Andrey Karitskiy ◽  
Yevgeniy Demin ◽  
...  

Psychological rehabilitation is an integral part of rehabilitation of a cancer patient. Psychological rehabilitation is aimed at a patient adaptation in the situation of the disease and improvement his quality of life. Understanding of an oncological disease is extreme and (or) crisis situation and monitoring dynamics of the psychological statement of a patient allows using differentiated approach in the provision of professional psychological assistance. The modified scale of self-esteem level of distress (IPOS) was used for screening of mental and emotional stress of cancer patients. There were selected groups of cancer patients who were most in need of professional psychological assistance. Results of a psychological study of one of these groups - breast cancer patients - are presented.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sanne Løkkegaard ◽  
Daniel Elias ◽  
Carla L. Alves ◽  
Martin V. Bennetzen ◽  
Anne-Vibeke Lænkholm ◽  
...  

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.


Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.


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