Parallel Assessment of Circulatory Cell-Free DNA by PCR and                     Nucleosomes by ELISA in Breast Tumors

Objectives In order to assess the potential biomolecules for breast cancer, we analyzed in parallel the levels of cell-free glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and cell-free nucleosomes in serum samples from patients with benign and malignant breast tumors. The levels of cell-free DNA obtained by quantitative PCR were compared with those obtained by enzyme-linked immunosorbent assay (ELISA). Methods Twenty-three patients with benign breast tumors, 27 patients with breast cancer, and 32 age-matched healthy women were recruited. The amounts of serum nucleosomes were analyzed by ELISA and the levels of cell-free GAPDH were measured by real-time quantitative PCR. The correlation between nucleosome and cell-free GAPDH levels was examined using the Spearman rank test. Results The levels of cell-free GAPDH were significantly higher in the serum samples of patients with benign and malignant breast tumors than in those of the control group (median 37,966 GE/mL, range 3,802–130,104 versus 11,770 GE/mL, range 2,198–73,522, p=0.035 and median 40,698 GE/mL, range 3,644–192,482 versus 11,770 GE/mL range 2,198–73,522, p=0.001). The concentration of cell-free GAPDH correlated significantly with the quantities of nucleosomes in serum samples (r=0.451, p=0.000). There was, however, no significant difference between healthy individuals and women with benign breast tumors or breast cancer in terms of nucleosomes determined by ELISA. Conclusion Our data suggest that the cell-free serum GAPDH DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA in patients with breast tumors.

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Sex Steroid Hormones in Serum and Tissue of Benign and Malignant Breast Tumor Patients

Disease Markers ◽

10.1155/2000/305940 ◽

2000 ◽

Vol 16 (3-4) ◽

pp. 151-157 ◽

Cited By ~ 22

Author(s):

Essam A. Mady ◽

Ezz El-Din H. Ramadan ◽

Alaa A. Ossman

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Steroid Hormones ◽

Breast Tumor ◽

Tumor Tissue ◽

Breast Tumors ◽

Sex Steroid ◽

Malignant Breast Tumor ◽

Malignant Breast ◽

Benign Breast Tumors

The ability of breast tumors to synthesize sex steroid hormones is well recognized and their local production is thought to play a role in breast cancer development and growth. The aim of this study was to estimate local intra-tumoral and circulating levels of Estrone (E1), Estrone Sulfate (E1S), Estradiol (E2), Estriol (E3), and Testosterone (T) in 33 pre- and postmenopausal women with primary breast cancer in comparison to 12 pre- and postmenopausal women with benign breast tumors. The mean levels of the studied sex hormones were higher in serum and tumor tissue of breast cancer women than those with benign breast tumors apart from Testosterone which showed a significant decrease in pre- and postmenopausal women with breast cancer (P< 0.001 for follicular phase,P< 0.001 for luteal phase, andP< 0.001 for postmenopausal). The levels of the five hormones were significantly higher intra-tumoral than in serum of both benign and malignant breast tumor women with E1S as the predominant estrogen. There was only a positive significant correlation between serum and tumor tissue levels of E1(rs= 0.52,P< 0.05 for follicular;rs= 0.63,P< 0.05 for luteal andrs= 0.58,P< 0.05 for postmenopausal) and a significant correlation between serum and tumor tissue of T (rs= 0.64,P< 0.05 for follicular;rs= -0.51,P< 0.05 for luteal andrs= -0.81,P< 0.04 for postmenopausal).

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Profile of anterior gradient 3 (AGR3) mRNA expression and serum levels in benign and malignant breast tumors

Breast Disease ◽

10.3233/bd-219006 ◽

2021 ◽

pp. 1-5

Author(s):

Prihantono Prihantono ◽

Warsinggih Rahardjo ◽

Salman Ardi Syamsu ◽

Nilam Smaradhania

Keyword(s):

Breast Cancer ◽

Mrna Expression ◽

Serum Protein ◽

Breast Tumors ◽

Serum Levels ◽

Protein Levels ◽

Qrt Pcr ◽

Potential Biomarker ◽

Significant Difference ◽

Malignant Breast

BACKGROUND: Benign and malignant breast tumors are the most commonly diagnosed tumor in females. Early and accurate diagnosis of malignancy is essential for effective breast cancer treatment. Human anterior gradient 3 (AGR3) has been suggested as a potential biomarker for the early detection and prognostic determination of breast cancer. OBJECTIVE: This study profiles AGR3 mRNA expression and serum protein levels in patients with benign and malignant breast tumors. METHODS: A case-control study was conducted on 40 benign and 40 malignant breast tumor patients in Makassar, Indonesia. AGR3 mRNA and protein were detected using qRT-PCR and ELISA, respectively. RESULTS: This study found significantly higher AGR3 mRNA expression in benign than malignant breast tumors using qRT-PCR (p < 0.001). In contrast, ELISA revealed no significant difference between AGR3 serum protein levels in benign and malignant breast tumors (p = 0.507). CONCLUSIONS: AGR3 is associated with non-aggressive tumors and could be used as a marker for less aggressive breast tumors.

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Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.6.1848 ◽

1996 ◽

Vol 14 (6) ◽

pp. 1848-1857 ◽

Cited By ~ 155

Author(s):

N Avril ◽

J Dose ◽

F Jänicke ◽

S Bense ◽

S Ziegler ◽

...

Keyword(s):

Breast Cancer ◽

Pet Imaging ◽

Breast Imaging ◽

Breast Tumors ◽

Partial Volume Correction ◽

Partial Volume ◽

Volume Correction ◽

Fdg Uptake ◽

Significant Difference ◽

Malignant Breast

PURPOSE To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.

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SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer

Clinical Chemistry ◽

10.1373/clinchem.2012.191551 ◽

2013 ◽

Vol 59 (1) ◽

pp. 270-279 ◽

Cited By ~ 80

Author(s):

Maria Chimonidou ◽

Areti Strati ◽

Nikos Malamos ◽

Vasilis Georgoulias ◽

Evi S Lianidou

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Early Breast Cancer ◽

Promoter Methylation ◽

Breast Tumors ◽

Surgical Removal ◽

Healthy Individuals ◽

Cell Free Dna ◽

Free Dna

INTRODUCTION Detection of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in the peripheral blood of patients with solid tumors has been widely studied for the early detection of metastatic spread. We evaluated whether there was an association between the origin of cfDNA and CTCs. We investigated whether SRY (sex determining region Y)-box 17 (SOX17) promoter methylation in CTCs was associated with the methylation pattern of this gene in matched cfDNA isolated from plasma of patients with breast cancer. METHODS We examined SOX17 methylation in 79 primary breast tumors, in 114 paired samples of DNA isolated from CTCs and cfDNA, and in 60 healthy individuals. Isolated DNA was modified by sodium bisulfite and subjected to methylation specific PCR. RESULTS The SOX17 promoter was methylated in 68 (86.0%) of 79 of primary breast tumors. In CTCs, SOX17 was methylated in 19 (34.5%) of 55 patients with early breast cancer, 27 (45.8%) of 59 patients with metastatic cancer, and 1 (4.3%) of 23 healthy individuals, whereas in matched cfDNA SOX17 was methylated in 19 (34.5%) of 55, 24 (40.7%) of 59, and 1 (2.0%) of 49 of these same groups, respectively. There was a significant correlation between SOX17 methylation in cfDNA and CTCs in patients with early breast cancer (P = 0.008), but not in patients with verified metastasis (P = 0.283). CONCLUSIONS The SOX17 promoter is highly methylated in primary breast tumors, in CTCs isolated from patients with breast cancer, and in corresponding cfDNA samples. Our findings indicate a direct connection between the presence of CTCs and cfDNA in patients with operable breast cancer, after surgical removal of the primary tumor.

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Assessment of IL17BR serum concentration in females with benign & malignant breast tumors

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1313 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Haider Abed Ali Alshawi

Keyword(s):

Breast Cancer ◽

Age Groups ◽

Breast Tumors ◽

Recurrent Breast Cancer ◽

Significant Difference ◽

Malignant Breast ◽

Healthy Control ◽

Study Population ◽

The Mean ◽

Recurrent Breast

Breast cancer is one of the most dangerous and most common malignanciesamong women in the world, which affects different age groups of women, IL-17 plays an important role in chronic inflammation and cancer, Serum IL-17BR concentration which useful in early diagnosis and staging of breast tumors.The aim of the study was to evaluate of IL-17BR serum concentrations in patients with benign and malignant breast tumors and study the relation between the above parameter and breast cancer development. The study population was composed of 120 samples 24 patients with recently diagnosed breast carcinoma,6 patients with repetitive carcinoma,40 patients with benign breast tumor (fibroadenoma) and 50 normal apparently health woman as a control.ELISA technique was applied for estimation of IL-17BR levels in patients as well as apparently healthy volunteers of women. The results revealed the mean age of malignant breast females was 52.8 ± 12.3 (Mean ± SD),while it was 26.9 ± 8.3 years for women with benign tumor with highly significant difference(P<0.001),IL-17BR level was determined and found that was a highly significant difference in its level among benign breast females subjects (72.48 Ng/ μL) and healthy control (50.87 Ng/ μL) P< 0.001),no significant difference in the mean of sIL-17BR level among the different patients‘ groups (49.83,64.33 Ng/ μL) for recurrent and primary breast cancer respectively.Estimation of IL-17BR level showed significant elevation of the concentration among the sera of recurrent breast cancer in comparison with other groups which perhaps regarded as a prognostic marker.

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Levels of Circulating Cell-Free Serum DNA in Benign and Malignant Breast Lesions

The International Journal of Biological Markers ◽

10.1177/172460080702200202 ◽

2007 ◽

Vol 22 (2) ◽

pp. 95-99 ◽

Cited By ~ 18

Author(s):

R.A. Zanetti-Dällenbach ◽

S. Schmid ◽

E. Wight ◽

W. Holzgreve ◽

A. Ladewig ◽

...

Keyword(s):

Benign Breast Disease ◽

Breast Disease ◽

Diagnostic Value ◽

Breast Lesions ◽

Healthy Individuals ◽

Serum Samples ◽

Cell Free Dna ◽

Free Dna ◽

Malignant Breast ◽

Circulating Cell Free Dna

Purposes of the study: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. Basic procedures: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. Main findings: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. Principal conclusion: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.

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Serum cell-free DNA concentration in BALB/c mice with azoxymethane-dextran sodium sulfate-induced colorectal cancer

Medical Journal of Indonesia ◽

10.13181/mji.v24i1.730 ◽

2015 ◽

Vol 24 (1) ◽

pp. 3-7

Author(s):

Virhan Novianry ◽

Yulhasri Yulhasri ◽

Kusmardi Kusmardi

Keyword(s):

Colorectal Cancer ◽

Sodium Sulfate ◽

The United States ◽

Dextran Sodium Sulfate ◽

Colorectal Carcinogenesis ◽

Serum Samples ◽

Cell Free Dna ◽

The Third ◽

Free Dna ◽

Significant Difference

Background: Colorectal cancer is the third most common cancer in the United States with a mortality rate ranked second in 2012. Early diagnosis such as detection of DNA in serum or faeces at the polyp stage, will reduce colorectal cancer mortality. This study was conducted to analyze the concentration of cell-free DNA (cfDNA) as a tumor marker in colorectal carcinogenesis by using blood serum samples from BALB/c mice previously induced by azoxymethane (AOM) and promoted by dextran sodium sulfate (DSS).Methods: This experimental animal study used 6 BALB/c mice which had serial intervention in a certain time frame. The first serum samples were taken before induction of carcinogenesis (week-0); then AOM induction of carcinogenesis followed and the second sampling one week after AOM intervention (week-1). Subsequently, promotion of carcinogenesis followed with DSS and the third sampling one week after this intervention (week-2). The fourth sampling was 5 weeks after AOM-DSS intervention (week-6). Quantification of the serum cfDNA was performed with SYBR-Green II fluorescence using Rotor Gene 6000 as a reference. Histopathological examination verified induction of carcinogenesis. For statistical analysis paired T-test was used.Results: Concentration of serum cfDNA showed significant difference between sampling group at week-0 (1238.49 ± 674.84 pg/µL) and sampling group at week-6 (2244.04 ± 726.57 pg/µL) the latter group showing pre-cancerous histopathology. Slightly increased cfDNA at week-1 with AOM induction (1358.57 ± 803.81 pg/µL) and week-2 after DSS promotion (1317.23 ± 735.92 pg/µL) were not significantly different from week-0 samples.Conclusion: The concentration of cfDNA in the serum of BALB/c mice 5 weeks after AOM induction of carcinogenesis and DSS promotion is significantly higher than before induction.

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