scholarly journals C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients

Author(s):  
Emilia Dąbrowska ◽  
Andrzej Przylipiak ◽  
Monika Zajkowska ◽  
Barbara Maria Piskór ◽  
Aleksandra Borowik-Zaręba ◽  
...  

The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients’ plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I – 0.7089; stage II – 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Charalampos Seretis ◽  
Fotios Seretis ◽  
Emmanuel Lagoudianakis ◽  
Marianna Politou ◽  
George Gemenetzis ◽  
...  

Background. The objective of our study is to investigate the potential effect of adjusting preoperative platelet to lymphocyte ratio, an emerging biomarker of survival in cancer patients, for the fraction of large platelets.Methods. A total of 79 patients with breast neoplasias, 44 with fibroadenomas, and 35 with invasive ductal carcinoma were included in the study. Both conventional platelet to lymphocyte ratio (PLR) and the adjusted marker, large platelet to lymphocyte ratio (LPLR), were correlated with laboratory and histopathological parameters of the study sample.Results. LPLR elevation was significantly correlated with the presence of malignancy, advanced tumor stage, metastatic spread in the axillary nodes and HER2/neu overexpression, while PLR was only correlated with the number of infiltrated lymph nodes.Conclusions. This is the first study evaluating the effect of adjustment for large platelet count on improving PLR accuracy, when correlated with the basic independent markers of survival in a sample of breast cancer patients. Further studies are needed in order to assess the possibility of applying our adjustment as standard in terms of predicting survival rates in cancer.


2017 ◽  
Author(s):  
Lucy Ireland ◽  
Almudena Santos ◽  
Fiona Campbell ◽  
Carlos Figueiredo ◽  
Lesley Ellies ◽  
...  

ABSTRACTBreast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours. 75% of breast cancer patients show activation of Insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in a pre-clinical breast cancer model compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.


1997 ◽  
Vol 15 (11) ◽  
pp. 3363-3367 ◽  
Author(s):  
M L Disis ◽  
S M Pupa ◽  
J R Gralow ◽  
R Dittadi ◽  
S Menard ◽  
...  

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population. RESULTS The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of > or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P < .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). CONCLUSION The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1526-1526
Author(s):  
R. Haque ◽  
J. E. Schottinger ◽  
M. H. Kanter ◽  
C. C. Avila ◽  
R. Contreras ◽  
...  

1526 Background: Kaiser Permanente Southern California (KPSC) led the nation in screening women for breast cancer (BCa) with a mammography rate of nearly 90% in 2007 according to 2008 Healthcare Effectiveness Data and Information Set (HEDIS) measures. Despite successes in improving screening rates in this health plan that serves 3+ million diverse members, the percentage of women diagnosed with late stage BCa (stage III, IV) remained stable, varying from 12.9% (N∼323) in 2003 to 10.8% (N∼270) in 2007. To identify patient and health care factors associated with late stage diagnosis and the impact of its enhanced screening implementation guidelines, KPSC undertook this study. Methods: This cross-sectional study included a cohort of 10,580 BCa patients from 2003–2007. We compared women diagnosed with late stage disease versus those with early stage disease (stages I, II). P values (2-sided) were based on the chi-square distribution. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. Results: Factors that were positively associated with late stage diagnosis in the univariate analyses included age, lack of recent mammography screening, worse tumor features, 80+ years of age, minority race, lower geocoded household income, increased healthcare visits, and use of Pap testing (P < 0.01 for all variables). Factors significantly associated with late stage diagnosis in the multivariate model included only lack of recent mammography screening (OR = 1.35, 95% CI: 1.14–1.58) and worse tumor features including high grade (grade 3, OR = 2.58, 95% CI: 1.96–3.40), positive lymph nodes (OR = 53.49, 95% CI: 39.90–71.72), and HER-2+ tumors (OR = 1.40, 95% CI: 1.13–1.72). Conclusions: Targeting older women, those with lower utilization, and women who did not have a recent mammogram may help further lower the prevalence of late stage diagnoses. However, given the extent of the health plan's previous efforts to enhance BCa screening rates, a ceiling effect may limit additional benefit. Additional efforts to decrease the rate of advanced tumor stage at diagnosis may include improving interpretation of mammograms or earlier detection of aggressive tumors by enhanced BRCA genetic testing. No significant financial relationships to disclose.


Author(s):  
Adnan M. Ismail ◽  
Eman S Saleh

Breast cancer is a disease in which cells in the breast grow out of control. CD200 is a cell surface glycoprotein expressed on many cells, it belongs to the immunoglobulin family (Ig) and have a great role in the regulation of inflammation in autoimmunity. CD200 is the ligand for CD200R1 receptor. To determine if serum level of CD200 and its receptor CD200R1 can be used as a diagnostic and prognostic marker in patients with breast cancer.This case control study was carried out at Oncology Teaching Hospital – Medical city in Baghdad. Six groups were enrolled, four groups were confirmed with breast cancer stage (I, II, III and IV), fifth group (benign) and sixth group was control (healthy individual). Serum is divided to measure CD200 and CD200R1 by utilizing quantitative sandwich enzyme-linked immunosorbent assay (ELISA) Kits. Serum level of CD200 was significantly different (P=0.000088) between breast cancer patients and control only, serum level of CD200 increases with disease stage and there is a significant positive correlation. Serum level of CD200R1 was different with stage, although the differences were not significant but the level of CD200R1 is lower in stage 4 patients than other stages. Serum CD200 level can be used as a diagnostic marker for breast cancer. Serum level of CD200R1 can be used as a prognostic marker


Breast Cancer ◽  
2021 ◽  
Author(s):  
Patrick Lebok ◽  
Hannah Bönte ◽  
Martina Kluth ◽  
Christina Möller-Koop ◽  
Isabell Witzel ◽  
...  

Abstract Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zhihao Fang ◽  
Yiqiu Hu ◽  
Jiani Chen ◽  
Kailun Xu ◽  
Kailai Wang ◽  
...  

RNA methylation plays a significant regulatory role in various of physiological activities and it has gradually become a hotspot of epigenetics in the past decade. 2′-O-methyladenosine (Am), 2′-O-methylguanosine (Gm), 2′-O-methylcytidine (Cm), 2′-O-methyluridine (Um), N6-methyladenosine (m6A), N1-methylguanosine (m1G), 5-methylcytidine (m5C), and 5-methyluridine (m5U) are representative 2′-O-methylation and base-methylation modified epigenetic marks of RNA. Abnormal levels of these ribonucleosides were found to be related to various diseases including cancer. Serum is an important source of biofluid for the discovery of biomarkers, and novel tumor biomarkers can be explored by measuring these ribonucleoside modifications in human serum. Herein, we developed and applied a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method to determine the content of monomethylated ribonucleosides in human serum. The developed method enabled sensitive and accurate determination of these monomethylated ribonucleosides. By applying this robust method, we demonstrated the presence of Gm and Um in human serum for the first time, and we successfully quantified m6A, Gm, m1G, Cm, Um and m5U in serum samples collected from 61 patients with breast cancer and 69 healthy controls. We discovered that the levels of Gm, m1G, Cm, Um and m5U in serum were all significantly decreased in breast cancer patients whereas m6A was increased. We performed receiver operating characteristic (ROC) curve analysis, and obtained highest area under curve (AUC) value when combining these six monomethylated ribonucleosides together. These results suggest that m6A, Gm, m1G, Cm, Um and m5U might have great potential to be novel biomarkers for detection of breast cancer in the early stage. In addition, this study may stimulate future investigations about the regulatory roles of monomethylated ribonucleosides on the initiation and development of breast cancer.


2016 ◽  
Vol 55 (01) ◽  
pp. 15-20 ◽  
Author(s):  
J. Farahati ◽  
A. G. Müller ◽  
E. Gillman ◽  
M. Hentschel ◽  
F. H. H. Müller

SummaryAim: To evaluate the diagnostic value (sensitivity, specificity) of positron emission mammography (PEM) in a single site non-interventional study using the maximum PEM uptake value (PUVmax). Patients, methods: In a singlesite, non-interventional study, 108 patients (107 women, 1 man) with a total of 151 suspected lesions were scanned with a PEM Flex Solo II (Naviscan) at 90 min p.i. with 3.5 MBq 18F-FDG per kg of body weight. In this ROI(region of interest)-based analysis, maximum PEM uptake value (PUV) was determined in lesions, tumours (PUVmaxtumour), benign lesions (PUVmaxnormal breast) and also in healthy tissues on the contralateral side (PUVmaxcontralateral breast). These values were compared and contrasted. In addition, the ratios of PUVmaxtumour / PUVmaxcontralateral breast and PUVmaxnormal breast / PUVmaxcontralateral breast were compared. The image data were interpreted independently by two experienced nuclear medicine physicians and compared with histology in cases of suspected carcinoma. Results: Based on a criteria of PUV>1.9, 31 out of 151 lesions in the patient cohort were found to be malignant (21%). A mean PUVmaxtumour of 3.78 ± 2.47 was identified in malignant tumours, while a mean PUVmaxnormal breast of 1.17 ± 0.37 was reported in the glandular tissue of the healthy breast, with the difference being statistically significant (p < 0.001). Similarly, the mean ratio between tumour and healthy glandular tissue in breast cancer patients (3.15 ± 1.58) was found to be significantly higher than the ratio for benign lesions (1.17 ± 0.41, p < 0.001). Conclusion: PEM is capable of differentiating breast tumours from benign lesions with 100% sensitivity along with a high specificity of 96%, when a threshold of PUVmax >1.9 is applied.


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