Blood Circulating Exosomes Contain Distinguishable Fractions of Free and Cell-Surface-Associated Vesicles

Background: Considering exosomes as intercellular transporters, inevitably interacting with the plasma membrane and the large available surface of blood cells, we wonder if a fraction of circulating exosomes is associated with the surface of blood cells. Objective: The aim of this study was to develop an efficient protocol for isolating exosomes associated with the surface of blood cells and to further investigate the characteristics of this fraction in a healthy state and during the development of breast cancer, as well as its possible implication for use in diagnostic applications. Methods: Blood samples were collected from Healthy Females (HFs) and breast cancer patients (BCPs). Exosomes extracted from blood plasma and eluted from the surface of blood cells were isolated by ultrafiltration with subsequent ultracentrifugation. Results: Transmission Electron Microscopy (TEM), along with immunogold labeling, demonstrated the presence of exosomes among membrane-wrapped extracellular vesicles (EVs) isolated from both plasma and blood cell eluates. TEM, nanoparticle tracking analysis, and NanoOrange protein quantitation data showed that cell-associated exosomes constituted no less than 2/3 of total blood exosome number. Exosomes, ranging from 50–70 nm in size, prevailed in the blood of breast cancer patients, whereas smaller exosomes (30–50 nm) were mostly observed in the blood of healthy women. Analysis of specific proteins and RNAs in exosomes circulating in blood demonstrated the significant differences in the packing density of the polymers in exosomes of HFs and BCPs. Preliminary data indicated that detection of cancer-specific miRNA (miR-103, miR-191, miR-195) in exosomes associated with the fraction of red blood cells allowed to discriminate HFs and BCPs more precisely compared to cell-free exosomes circulating in plasma. Conclusion: Our data provide the basis for using blood cell-associated exosomes for diagnostic applications.

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Correlation Between TILs and Blood Cell Counts in Triple Negative Breast Cancer Patients

Case Medical Research ◽

10.31525/ct1-nct04068623 ◽

2019 ◽

Author(s):

Keyword(s):

Breast Cancer ◽

Blood Cell ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Patients ◽

Cell Counts ◽

Blood Cell Counts

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A Pilot Study: Application of Hemoglobin and Cortisol Levels, and A Memory Test to Evaluate the Quality of Life of Breast Cancer Patients on Chemotherapy

The International Journal of Biological Markers ◽

10.5301/jbm.5000053 ◽

2013 ◽

Vol 28 (4) ◽

pp. 348-356 ◽

Cited By ~ 1

Author(s):

Wings TY Loo ◽

Michael CW Yip ◽

Louis WC Chow ◽

Qing Liu ◽

Elizabeth LY Ng ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Cancer Patients ◽

Blood Cells ◽

Healthy Subjects ◽

Short Term Memory ◽

White Blood Cells ◽

Breast Cancer Patients ◽

Cortisol Levels

Background Short-term memory (STM) decline in breast cancer patients resulting from chemotherapy was evaluated by means of blood biomarkers, a questionnaire, and a computerized STM test. Methods This study was conducted from January 2013 to June 2013, recruiting 90 subjects: 30 breast cancer patients beginning the 3rd of 4th cycles of docetaxel and cyclophosphamide chemotherapy, 30 recovered patients (who completed 4 cycles of docetaxel for a minimum of 6 months), and 30 healthy subjects (disease-free females). The levels of hemoglobin, red and white blood cells, and cortisol in serum, and a computerized STM test were analyzed to estimate the effects of chemotherapy on STM. A questionnaire was given to all subjects to assess quality of life. Results Statistically significant differences were observed for the blood parameters (hemoglobin, red and white blood cells, and cortisol levels) between healthy and on-treatment subjects (respectively 13.47±0.96 g/dL vs 5.37±0.38 g/dL, 4.58±0.41 1012/L vs 2.07±0.13 1012/L, and 6.15±1.03 109/L vs 0.86±0.41 109/L). Scores of the STM test were significantly lower for patients compared to healthy subjects. As indicated by the results of the questionnaire, breast cancer patients had a higher tendency to forget than healthy controls (X2=3.15; p<0.0001) and recovered subjects (X2=3.15; p<0.0001). Conclusion We found depleted levels of hemoglobin, red and white blood cells as a result of chemotherapy, and elevated levels of stress correlated with poor performances in the computerized STM test. A higher cortisol level might be an important precursor of STM deterioration. Monitoring cortisol would be beneficial for evaluating the quality of life of breast cancer patients on chemotherapy.

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Systemic NF-κB activation in blood cells of breast cancer patients

Redox Report ◽

10.1179/135100006x101002 ◽

2006 ◽

Vol 11 (1) ◽

pp. 39-44 ◽

Cited By ~ 10

Author(s):

Miroslav Adžić ◽

Ana Nićiforović ◽

Vesna Vučić ◽

Zora Nešković-Konstantinović ◽

Snežana D. Spasić ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Blood Cells ◽

Breast Cancer Patients

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Combining contrast-enhanced ultrasound and blood cell analysis to improve diagnostic accuracy of plasma cell mastitis

Experimental Biology and Medicine ◽

10.1177/15353702211049361 ◽

2021 ◽

pp. 153537022110493

Author(s):

Yan Zheng ◽

Lin Wang ◽

Xiu Han ◽

Lin Shen ◽

Chen Ling ◽

...

Keyword(s):

Breast Cancer ◽

Blood Cell ◽

Diagnostic Accuracy ◽

Cancer Patients ◽

Plasma Cell ◽

Perfusion Defect ◽

Cell Analysis ◽

Contrast Enhanced Ultrasound ◽

Breast Cancer Patients ◽

Contrast Enhanced

Plasma cell mastitis is a benign suppurative disease of the breast, lack of specific clinical manifestations, which is easy to be misdiagnosed and mistreated, often confused with mastitis, breast cancer (BC), and other diseases. Thus, we aimed to establish a combined model of promoting diagnostic accuracy of plasma cell mastitis by contrast-enhanced ultrasound (CEUS) patterns and routine blood cell analysis. Eighty-eight plasma cell mastitis, 91 breast cancer, and 152 other benign breast diseases’ patients grouped according to pathological diagnosis underwent CEUS and blood cell analysis examination; 100 healthy female donors were involved. All the plasma cell mastitis and breast cancer patients presented hyperenhancement of CEUS breast lesions compared with others. The majority of plasma cell mastitis (65/88) showed perfusion defect of CEUS patterns with smooth edge (56/65) and multiple lesions (49/65); in contrast, fewer breast cancer patients (30/91) displayed perfusion defect. White blood cell count (WBC), neutrophils, and neutrophils/lymphocytes ratio of blood cell analysis in plasma cell mastitis patients increased significantly compared with other patients ( P < 0.0001). Combining perfusion defect of CEUS patterns and WBC yielded an area under the receiver operating characteristic curve of 0.831, higher than single 0.720 and 0.774, respectively. The cut-off value of WBC (7.28 × 109/L) helped remaining 65.2% (15/23) atypical cases to be correctly diagnosed as plasma cell mastitis, not misdiagnosed as breast cancer. In conclusion, CEUS presented a clear perfusion defect pattern of plasma cell mastitis lesion for the first time. A precise WBC by routine blood cell analysis test can assist CEUS examination in the differential diagnosis of plasma cell mastitis and breast cancer. It is a promised combination for laboratory diagnostic of PCM.

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Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21197341 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7341

Author(s):

Maria Konoshenko ◽

Georgy Sagaradze ◽

Evgeniya Orlova ◽

Tatiana Shtam ◽

Ksenia Proskura ◽

...

Keyword(s):

Breast Cancer ◽

Cell Surface ◽

Blood Cell ◽

Cancer Patients ◽

Path Length ◽

Total Blood ◽

Migration Path ◽

Mesenchymal Transition ◽

Tumor Dissemination ◽

Total Migration

Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used.

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Altered Levels of Desaturation and ω-6 Fatty Acids in Breast Cancer Patients’ Red Blood Cell Membranes

Metabolites ◽

10.3390/metabo10110469 ◽

2020 ◽

Vol 10 (11) ◽

pp. 469

Author(s):

Javier Amézaga ◽

Gurutze Ugartemendia ◽

Aitziber Larraioz ◽

Nerea Bretaña ◽

Aizpea Iruretagoyena ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Fatty Acid ◽

Blood Cell ◽

Cancer Patients ◽

Red Blood Cell ◽

Breast Cancer Patients ◽

Disease Evolution ◽

Lipidomic Analysis ◽

Rbc Membrane

Red blood cell (RBC) membrane can reflect fatty acid (FA) contribution from diet and biosynthesis. In cancer, membrane FAs are involved in tumorigenesis and invasiveness, and are indicated as biomarkers to monitor the disease evolution as well as potential targets for therapies and nutritional strategies. The present study provides RBC membrane FA profiles in recently diagnosed breast cancer patients before starting chemotherapy treatment. Patients and controls were recruited, and their dietary habits were collected. FA lipidomic analysis of mature erythrocyte membrane phospholipids in blood samples was performed. Data were adjusted to correct for the effects of diet, body mass index (BMI), and age, revealing that patients showed lower levels of saturated fatty acids (SFA) and higher levels of monounsaturated fatty acid, cis-vaccenic (25%) than controls, with consequent differences in desaturase enzymatic index (∆9 desaturase, –13.1%). In the case of polyunsaturated fatty acids (PUFA), patients had higher values of ω-6 FA (C18:2 (+11.1%); C20:4 (+7.4%)). RBC membrane lipidomic analysis in breast cancer revealed that ω-6 pathways are favored. These results suggest new potential targets for treatments and better nutritional guidelines.

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Longterm blood cell counts after intraoperative radiotherapy with or without whole breast radiotherapy in breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12014 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12014-e12014

Author(s):

Elena Sperk ◽

Cornelia Wersal ◽

Christel Weiss ◽

Anke Keller ◽

Anette Kipke ◽

...

Keyword(s):

Breast Cancer ◽

Blood Cell ◽

Cancer Patients ◽

Cell Lines ◽

Breast Cancer Patients ◽

Breast Radiotherapy ◽

Cell Counts ◽

Blood Cell Counts ◽

Whole Breast Radiotherapy

e12014 Background: After radiotherapy changes in blood cell counts (BCC) can be seen. Leukocytopenia may have a negative impact on the immune system, outcome and quality of life of breast cancer survivors. No reports on changes of the three blood cell lines (leukocytes=WBC, erythrocytes=RBC, thrombocytes=PLT) after IORT w/o whole breast radiotherapy (WBRT) in breast cancer patients have been reported. Methods: 256 patients had IORT during breast conserving surgery. In 198 patients WBRT (46-50Gy/2Gy) + IORT (20Gy) and in 58 patients IORT as accelerated partial breast irradiation=APBI (20Gy) was given. Preoperative BCC were used as baseline. In 214 patients BCC were available after 1-90 days, in 139 during the 1st year, in 86 in the 2nd, in 66 in the 3rd, in 51 in the 4th and in 34 in the 5th year of follow-up. Dunnett-tests were used to calculate adjusted p-values (p<0.05=significant). Results: After IORT/WBRT a decrease of WBC was seen during the 1st year. Afterwards no changes were seen. After IORT APBI no changes were seen during 5 years follow-up. RBC was decreased at all time points after IORT/WBRT, and through the 1st year after IORT APBI. PLT decreased during the 1st year and stayed low during 5 years after IORT/WBRT. No changes in PLT were seen after IORT APBI. Hemoglobin (HGB) decreased after 3 months, during the 1st and 5th year after IORT/WBRT. After IORT APBI, HGB decreased only during the 1st year and stayed stable during follow-up. Conclusions: Decreases of all blood cell lines were seen at least transiently after IORT/WBRT. PLT and RBC stayed decreased. After IORT APBI, HGB and RBC decreased only during the 1st year and WBC and PLT remained stable during the whole follow-up. [Table: see text]

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