scholarly journals Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

2017 ◽  
Vol 44 (5) ◽  
pp. 1741-1748 ◽  
Author(s):  
Xiu Juan Li ◽  
Zhao Jun Ren ◽  
Jin Hai Tang ◽  
Qiao Yu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Functional Significance ◽  
Metastatic Breast ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Cell Viability Assay ◽  
Exosomal Mirnas ◽  
Exosomal Microrna

Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

scholarly journals Successful Remission of Hemolytic-Uremic Syndrome during the Third-line Weekly Gemcitabine for Metastatic Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S14920
Author(s):  
Victor C. Kok ◽  
Sheng-Chung Wu ◽  
Chien-Kuang Lee
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hemolytic Uremic Syndrome ◽  
Cancer Progression ◽  
Palliative Chemotherapy ◽  
Metastatic Breast ◽  
Kidney Injury ◽  
Peripheral Blood Smear ◽  
Uremic Syndrome ◽  
Third Line

Sequential palliative chemotherapy for metastatic breast cancer incorporating weekly gemcitabine administered as three-weeks-on, one-week-off schedule is widely adopted throughout the East Asia region. Hemolytic-uremic syndrome (HUS) associated with weekly gemcitabine for a breast cancer patient is extremely rare. We report here a case of 43-year-old woman with metastatic breast cancer who received weekly gemcitabine as a third-line palliative chemotherapy for her disease. She developed HUS after a cumulative dose of 11,000 mg/m2 gemcitabine, evidenced by microangiopathic hemolytic anemia (MAHA) with schistocytes seen in peripheral blood smear, decreased haptoglobin level (<0.29 mmol/L), thrombocytopenia, negative direct Coombs test, and acute kidney injury. Owing to the ease of administration of weekly gemcitabine, gemcitabine-induced thrombocytopenia, multifactorial anemia in metastatic breast cancer, and possibility of cancer progression, HUS could have gone unnoticed. Breast cancer oncologist should be cognizant of this rare HUS even during weekly gemcitabine treatment.

scholarly journals A Model of Dormant-Emergent Metastatic Breast Cancer Progression Enabling Exploration of Biomarker Signatures

2018 ◽  
Vol 17 (4) ◽  
pp. 619-630 ◽  
Author(s):  
Amanda M. Clark ◽  
Manu P. Kumar ◽  
Sarah E. Wheeler ◽  
Carissa L. Young ◽  
Raman Venkataramanan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Breast Cancer Progression

scholarly journals Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?

2020 ◽  
Vol 10 (4) ◽  
pp. 227
Author(s):  
Maria Ida Amabile ◽  
Federico Frusone ◽  
Alessandro De Luca ◽  
Domenico Tripodi ◽  
Giovanni Imbimbo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Medical Treatment ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Treatment Decision ◽  
Careful Consideration ◽  
Level Of Evidence ◽  
Systemic Treatments ◽  
Metastatic Setting

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient’s global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.

scholarly journals Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1827 ◽  
Author(s):  
Grace L. Wong ◽  
Sara Abu Jalboush ◽  
Hui-Wen Lo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Metastatic Breast ◽  
Tumor Stroma ◽  
Breast Cancer Metastasis ◽  
Exosomal Mirnas ◽  
Made In

Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

Capture of EpCAM-negative and vimentin-positive circulating cancer cells (CCCs) from blood of metastatic breast cancer patients using ApoStream.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21029-e21029
Author(s):  
Christopher Neal ◽  
Sujita Sukumaran ◽  
Vishal Gupta ◽  
Insiya Jafferji ◽  
Dave Hasegawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Laser Scanning ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Circulating Cancer Cells

e21029 Background: Up-regulation of epithelial mesenchymal transition (EMT) and the reduction of epithelial marker expression is associated with invasion, cancer progression, resistance to conventional therapies and poor prognosis. ApoStream, a novel continuous flow dielectrophoresis field-flow fractionation (DEP-FFF) device, was used to enable antibody-independent capture of circulating cancer cells (CCCs,also referred to as circulating tumor cells, CTC) for subsequent phenotyping of EMT markers. Methods: A side-by-side comparison of CellSearch and ApoStream was performed on 10 metastatic breast cancer patients. A multiplexed immunofluorescent assay and laser scanning cytometry analyses were used to unambiguously identify CK+/CD45–/DAPI+ CCCs and quantify their EpCAM and vimentin expression. Results: ApoStream recovered CK+/CD45–/DAPI+ CCCs from each breast cancer patient sample tested (mean=255 CCCs per 7.5 ml blood, see Table). ApoStream consistently recovered significantly higher number of CCCs compared to CellSearch (p=0.024). ApoStream recovered both EpCAM+ and EpCAM– CCCs in 50% and 90% of patients, respectively. Vimentin+ CCCs were isolated from 90% of patients. Conclusions: ApoStream’s higher capture efficiency demonstrated the majority of CCCs from breast cancer patients were EpCAM negative and vimentin-positive. ApoStream technology can be used to monitor CCCs undergoing EMT. [Table: see text]

scholarly journals SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis

2016 ◽  
Vol 113 (3) ◽  
pp. 638-643 ◽  
Author(s):  
Sait Ozturk ◽  
Panagiotis Papageorgis ◽  
Chen Khuan Wong ◽  
Arthur W. Lambert ◽  
Hamid M. Abdolmaleky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Breast Cancer Progression ◽  
Metastasis Suppressor ◽  
Suppressor Genes ◽  
Metastasis Suppressor Genes ◽  
Model Cell

Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis–free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.

scholarly journals Decrease in Depression Symptoms Is Associated With Longer Survival in Patients With Metastatic Breast Cancer: A Secondary Analysis

2011 ◽  
Vol 29 (4) ◽  
pp. 413-420 ◽  
Author(s):  
Janine Giese-Davis ◽  
Kate Collie ◽  
Kate M.S. Rancourt ◽  
Eric Neri ◽  
Helena C. Kraemer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Secondary Analysis ◽  
Depression Scale ◽  
Metastatic Breast ◽  
Control Group ◽  
Depression Symptoms ◽  
First Year ◽  
Depression Symptom

Purpose Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival. Methods In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies–Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival. Results Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association. Conclusion Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis.

scholarly journals Widespread Alternative Splicing Changes in Metastatic Breast Cancer Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 858
Author(s):  
Jagyeong Oh ◽  
Davide Pradella ◽  
Changwei Shao ◽  
Hairi Li ◽  
Namjeong Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Alternative Splicing ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Expression Levels

Aberrant alternative splicing (AS) is a hallmark of cancer and a potential target for novel anti-cancer therapeutics. Breast cancer-associated AS events are known to be linked to disease progression, metastasis, and survival of breast cancer patients. To identify altered AS programs occurring in metastatic breast cancer, we perform a global analysis of AS events by using RNA-mediated oligonucleotide annealing, selection, and ligation coupled with next-generation sequencing (RASL-seq). We demonstrate that, relative to low-metastatic, high-metastatic breast cancer cells show different AS choices in genes related to cancer progression. Supporting a global reshape of cancer-related splicing profiles in metastatic breast cancer we found an enrichment of RNA-binding motifs recognized by several splicing regulators, which have aberrant expression levels or activity during breast cancer progression, including SRSF1. Among SRSF1-regulated targets we found DCUN1D5, a gene for which skipping of exon 4 in its pre-mRNA introduces a premature termination codon (PTC), thus generating an unstable transcript degraded by nonsense-mediated mRNA decay (NMD). Significantly, distinct breast cancer subtypes show different DCUN1D5 isoform ratios with metastatic breast cancer expressing the highest level of the NMD-insensitive DCUN1D5 mRNA, thus showing high DCUN1D5 expression levels, which are ultimately associated with poor overall and relapse-free survival in breast cancer patients. Collectively, our results reveal global AS features of metastatic breast tumors, which open new possibilities for the treatment of these aggressive tumor types.

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