The Study of Programmed Death-1 Receptor, Programmed Death-1 Ligand (Pd-1/Pd-L1) and Apoptosis in Breast Cancer Patients: A Potential Mechanism of Immune Escape

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 5-5
Author(s):  
S.A Ali ◽  
A.N El-Daly ◽  
A El-Sayed ◽  
H.G El-Shredy ◽  
G.A Fadaly
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Escape ◽  
Serum Levels ◽  
Control Group ◽  
Potential Mechanism ◽  
Breast Cancer Patients ◽  
Programmed Death ◽  
Programmed Death 1

Introduction: The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest.However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to evaluate the role of programmed death-1 receptor and programmed death ligand-1 (PD-1/PD-L1) expressing lymphocytes, monocytes and granulocytes, as potential mechanism of immune escape in breast cancer patients. Also, serum levels of Bcl-2 were analyzed among patients with different stages of breast cancer. Material and Methods: The study was conducted on a total of seventy-five females; fifty-five of them represented the breast cancer females at early (24 females) and advanced (31 females) stages and 20 ages matched female donors represented the control group. Patients were recruited from the Cancer Research and Management Department, Medical Research Institute, Alexandria University. Venous blood samples obtained from all females under study were used for determination of PD-1/PD-L1 expression using flowcytometry technique and measurement of Bcl-2 serum levels using ELISA technique. Results: Significantly higher expression levels of PD-L1 were found in patients with positive lymph node, advanced tumor stage, histological grade II, tumor size T2, ER, PR, Her-2 negativity and TNBC subtype. Whilst a general increase in PD-1 positive expression between the breast cancer patients and control group regarding percentage and MFI of positive PD-1 expressing monocytes and granulocytes. Also, the results showed a highly significant association between PD-1+ and PD-L1+ expression in early and advanced breast cancer patients (p<0.0001). There was a significant increase in the mean of Bcl-2 serum concentration in patients compared to healthy individuals. Finally, the results showed that Bcl-2 serum concentration correlated positively with positive PD-L1+ expressing granulocytes. While the correlation between serum Bcl-2 and PD-1+ expressing lymphocytes, monocytes and granulocytes did not show any statistical significance. Conclusions: Our study suggested that PD-L1 could serve as an important target for antibody based immunotherapies, especially in the TNBC, where treatment options are limited. The direct correlation between PD-L1+ expression and serum Bcl-2 concentration may explore a role of apoptotic machinery in the pathogenesis of breast cancer.

Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Abeer I Abd Elmagid ◽  
Hala Abdel Al ◽  
Wessam El Sayed Saad ◽  
Seham Kamal Mohamed
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Tnm Staging ◽  
Control Group ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Female Patients ◽  
Significant Difference ◽  
Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p &lt; 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p &gt; 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p &gt; 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

scholarly journals The role of serum 25-hydroxyvitamin D, ionized calcium and phosphorus in breast cancer females: A case-control study

2015 ◽  
Vol 4 (2) ◽  
pp. 228 ◽  
Author(s):  
Nadia Abd El Moneim ◽  
Taha Hewala ◽  
Mona Rashad ◽  
Yousria Moussa ◽  
Nehal Abu-Samra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Ionized Calcium ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Serum Ionized Calcium ◽  
Group Serum

<p><strong>Aim:</strong> To evaluate the diagnostic and prognostic value of serum 25- hydroxyvitamin D (25(OH) D), ionized calcium and phosphorus in comparison with serum CA15.3 as the most commonly used breast cancer marker.</p><p><strong>Participants and methods:</strong> This study was conducted on 45 breast cancer female patients with recently detected breast cancer before surgery and 45 apparently healthy female controls of matched age, menstrual and socioeconomic status as breast cancer patients group. Serum 25(OH) D, ionized calcium, phosphorus and CA15.3 were measured using ready-for-use commercially available kits.</p><p><strong>Results:</strong> Serum levels of 25(OH) D and ionized calcium in the breast cancer patients group were significantly lower than those of the control group, while serum levels of phosphorus and CA15.3 in breast cancer patients group were significantly higher than those of the control group. The area under the ROC curve for serum ionized calcium (81.7%) was significantly greater than that of 25(OH) D (75.3%), CA 15.3 (70.1%) and phosphorus (62.8%). The odd’s ratio of vitamin D was 0.0937 (95% CI=0.0311-0.2823), of ionized calcium was 0.0464 (95% CI=0.015-0.141) and of phosphorus was 2.6801(95% CI=1.1269- 6.3742) in breast cancer patients group. Serum phosphorus was significantly correlated with age and menopausal status of breast cancer patients.</p><p><strong>Conclusion:</strong> Our results suggest that serum ionized calcium and 25(OH) D were superior to serum CA15.3 and phosphorus for prediction of breast cancer. In addition, our results indicate that 25 (OH) D and calcium may decrease the risk for breast cancer incidence, while phosphorus may increase this risk. None of the assayed biomarkers has a prognostic role in breast cancer.</p>

scholarly journals S100A14 serum level and its correlation with prognostic factors in breast cancer

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Noor Al-Ashkar ◽  
Almoutassem Billah Zetoune
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Prognostic Significance ◽  
Serum Levels ◽  
Control Group ◽  
Study Group ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
Cross Sectional

Abstract Background Breast cancer is the most commonly occurring cancer in women worldwide. S100A14 is a novel important member of S100 proteins family. Its importance is due to its role in tumorigenesis and metastasis process. In this study, we aimed to determine serum levels of S100A14 protein in breast cancer patients and healthy individuals to know if it can be suggested as a new biomarker for breast cancer and to reveal whether it is correlated with cancer pathological features. Methods This cross-sectional study was performed in two groups: study group contains 46 breast cancer patients (29 metastatic and 17 non-metastatic) and control group contains 22 healthy women. Enzyme-linked immunoabsorbent assay was performed to determine S100A14 protein levels in samples. Pathological data were obtained for each patient. The data were statistically analyzed using Kruskal-Wallis H, Mann-Whitney U, and Spearman correlation tests. Results S100A14 serum levels were elevated in study group compared with control group (P < 0.05). S100A14 serum levels were significantly increased in distant breast cancer patients compared with regional breast cancer patients (P = 0.001). There was a strong positive correlation between serum S100A14 level and tumor grade (rs = 0.713, P < 0.001). Conclusion Our study indicated that S100A14 serum levels are elevated in breast cancer patients compared with control individuals. High S100A14 serum levels were correlated with poor tumor differentiation so it might have a prognostic significance for breast cancer tumors. The elevation of S100A14 levels in distant breast cancer patients suggests the ability of using serum S100A14 as a biomarker for detection of breast cancer metastasis.

scholarly journals Inherited thrombophilic risk factors in Serbian breast cancer patients

Genetika ◽  
2019 ◽  
Vol 51 (2) ◽  
pp. 463-472
Author(s):  
Iva Pruner ◽  
Branko Tomic ◽  
Marija Dragojevic ◽  
Maja Gvozdenov ◽  
Mirjana Kovac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Mthfr C677t ◽  
Control Group ◽  
Gene Variants ◽  
Breast Cancer Patients ◽  
Significant Difference

Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed.

Effect of Kaiso on immune signaling of breast cancer exosomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3088-3088
Author(s):  
Windy Marie Dean-Colomb ◽  
Shakir Ahmed ◽  
Balasubramanyanam Karanam ◽  
Honghe Wang ◽  
Melissa Davis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Cancer Patients ◽  
Immune Escape ◽  
European American ◽  
Breast Cancer Patients ◽  
Immune Signaling ◽  
Immune Profiling

3088 Background: Exosomes are communication vesicles that act as mediators of intracellular transfer of genetic information, an important role in intercommunication between tumor cells and immune cells. However, the mechanism underlining this cell-cell communication is not well understanding, particularly in African American breast cancer patients. Recently, our lab has demonstrated that Kaiso, a novel bi-modal transcription factor is highly expressed in African American breast cancer and notably, high Kaiso expression correlates with breast cancer aggressiveness and the disparity in survival outcomes of breast cancer patients of African American compared to European American patients. However, the differential expression and biological consequences of Kaiso in immune signaling of breast cancer exosomes has not been studied yet. Herein we demonstrate the biological role of Kaiso in immune signaling in breast cancer exosomes. Methods: In this study we utilized Nanostring immune profiling technology along with multiple in vitro and in vivo assays were used to study the role of Kaiso in breast cancer immune escape. Results: Nanostring pan cancer immune profiling demonstrated that European American breast cancer exosomes exhibited higher expression of TILs markers, T cell activation markers and CD8+T Cells markers compared to African American (p < 0.05, FDR), while we observed an increase in the expression of the anti-phagocytic molecule CD47 in breast cancer patient exosomes of African American compared to European American patients. In addition to that CD47 and SIRP-α (Signal Regulatory Protein) are highly expressed in Kaiso-scrambled MDA-MB-231 cells (sh-Scr) and exosomes, whereas THBS1, which is a regulator of CD47 expression and is regarded as angiogenesis inhibitor is significantly increased in sh-Kaiso MDA-231 cells and exosomes. Additionally, we observed that Kaiso directly binds methylated sequences in the promoter region of CD47 and THBS1 by ChIP assay. Furthermore, in vivo sh-Kaiso cells injected into athymic mice exhibited delayed tumor formation after four weeks with smaller tumor size as compared to sh-SCR cells (p < 0.05), and we observed higher expression of THBS1 with lower expression of CD47 and SIRP-α molecules by IHC and exosomes isolated from in vivo tumors (p < 0.05), indicating that Kaiso is associated with macrophage mediated immune escape. Conclusions: These findings demonstrate the important role of kaiso in immune signaling through exosomes which may be related with more aggressive cancer phenotype in breast cancer, especially in African Americans.

scholarly journals Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients

Nutrients ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 37 ◽  
Author(s):  
Rihwa Choi ◽  
Min-Ji Kim ◽  
Insuk Sohn ◽  
Serim Kim ◽  
Isaac Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Trace Elements ◽  
Trace Element ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Inductively Coupled Plasma ◽  
Serum Levels ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Trace Element Levels

The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using inductively coupled plasma mass spectrometry in Korean breast cancer patients before initiation of breast cancer treatment. Korean females without breast cancer served as a control group. Trace element levels were measured in the discovery cohort (n = 287) and were validated in an independent cohort (n = 142). We further investigated possible associations between trace element levels and the presence of lymph node metastasis, distant metastasis, or triple-negative breast cancer among breast cancer patients in subgroup analyses. Serum manganese and molybdenum levels were significantly higher (p < 0.05) in breast cancer patients than in controls. Serum copper levels were significantly higher in breast cancer patients with distant metastasis, while selenium levels were significantly lower. Other trace elements were neither significantly different between breast cancer patients and controls nor between subgroups of breast cancer patients. Our study provides insights about the potential roles and impacts of trace elements through an assessment of the associations between trace elements and breast cancer.

scholarly journals Determination of Some Trace Elements in Breast Cancer Serum by Atomic Absorption Spectroscopy

2016 ◽  
Vol 9 (1) ◽  
pp. 1 ◽  
Author(s):  
Safaa Sabri Najim
Keyword(s):  
Breast Cancer ◽  
Trace Elements ◽  
Atomic Absorption ◽  
Cancer Patients ◽  
Absorption Spectroscopy ◽  
Atomic Absorption Spectroscopy ◽  
Serum Levels ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Flame Atomic Absorption

In the breast cancer significant differences occurs in the normal distribution of the trace elements, playing an important role in carcinogenic process. The aim of this study was to investigate the serum levels of some trace elements (Chromium, Cadmium, Manganese, Cobalt, Nickel, Selenium, Zinc, Iron, Copper and Magnesium) by using flame atomic absorption spectroscopy (FAAS). The present study included 150 females, the participates were divided into two main groups, control group which consisted of 75 apparently healthy females, 75patients with breast cancer group .The serum levels of Chromium (tcal2.9631 ,ttab1.960), Cadmium (tcal2.0798 ,ttab1.960), Manganese (tcal18.5676, ttab1.960), Selenium (tcal2.2759,ttab1.960), Iron (tcal2.9296,ttab1.960), Copper (tcal4.0869, ttab1.960),Magnesium (tcal2.6648, ttab1.960), Cobalt (tcal3.8615 , ttab1.960) and Zinc (tcal7.0160, ttab1.960) were statistically significant higher in the breast cancer patients group than the control group. Similarly, Nickel (tcal1.5988,ttab1.960) levels showed significant lower level in breast cancer patients group. On the other hand, the higher levels of trace elements could lead to formation of free radicals or other reactive oxygen species. The evaluation of these trace elements in serum maybe used as helpful tool in diagnosis of the breast cancer.

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