scholarly journals Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149551 ◽  
Author(s):  
Cheng-Siang Lee ◽  
Nur Aishah Mohd Taib ◽  
Ali Ashrafzadeh ◽  
Farhana Fadzli ◽  
Faizah Harun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Perchloric Acid ◽  
Serum Proteins ◽  
C1 Inhibitor ◽  
Proteoglycan 4 ◽  
Molecular Indicators ◽  
Protease C1

Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
R. Lastra ◽  
A. Monasterio ◽  
I. Alvarez-Busto ◽  
J. Mayordomo ◽  
J. Algorta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Serum Proteins ◽  
Simultaneous Detection ◽  
Serum Biomarkers ◽  
Protein Chip ◽  
Differentially Expressed ◽  
Clinical Validation ◽  
Serum Samples ◽  
Screening Programs ◽  
Healthy Women

e22019 Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity < 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH. No significant financial relationships to disclose.

Prognostic Value of Mutations in TP53 and RAS Genes in Breast Cancer

2003 ◽  
Vol 18 (1) ◽  
pp. 49-53 ◽  
Author(s):  
E. Guerra ◽  
G. Vacca ◽  
B. Palombo ◽  
S. Alberti
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Statistical Power ◽  
Healthcare Systems ◽  
Therapeutic Strategies ◽  
Response To Therapy ◽  
Suppressor Genes ◽  
Ras Genes ◽  
Molecular Indicators

The identification of molecular indicators of higher risk for specific subgroups of cancer patients may allow to develop more aggressive therapeutic strategies aimed at cases with the highest likelihood of response. This would avoid unnecessary toxicity to patients and alleviate the burden of cancer care for healthcare systems. Activated oncogenes and mutated tumor suppressor genes are causal determinants of the appearance and progression of tumors in man. They therefore represent potential indicators of prognosis and/or response to therapy. However, even in cases of well-studied oncogenes and tumor suppressor genes such as TP53 and RAS, their attributed prognostic and predictive value is often based on studies of insufficient statistical power that often lead to conflicting conclusions. Findings in favor or against the use of TP53 and RAS as prognostic and predictive indicators in breast cancer are reviewed and discussed here.

scholarly journals The Effects of Individual Diet Therapy on Food Intake, Quality of Life, and Related Serum Proteins in Patients with Breast Cancer: A Randomized Clinical Trial

2021 ◽  
Author(s):  
Azadeh Fallah ◽  
Kiana Parnian ◽  
Hamid Abdolazimi ◽  
Sajjad Tezerji ◽  
Zohreh Mazloom
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Side Effects ◽  
Cancer Patients ◽  
Serum Proteins ◽  
Intervention Group ◽  
Diet Therapy ◽  
Control Group ◽  
Nutritional Needs

Background: In cancer patients, weight loss due to malnutrition has a significant impact on the patients’ treatment and quality of life. This study aimed to determine the appropriate therapeutic strategy to control the side effects of chemotherapy in patients with breast cancer to improve their health, quality of life, and nutritional status. Methods: In our prospective study, we examined gastric cancer patients who were Seventy patients undergoing chemotherapy were included and randomly divided into intervention (n=35) and control groups (n=35). The intervention group received an individualized diet according to their nutritional needs for eight weeks, and the control group received dietary advice on the side effects of chemotherapy. Malnutrition, nutritional barriers, and patients’ quality of life were evaluated by PG-SGA, nutritional barriers, and QLQ-C30 questionnaires. Serum proteins were also assessed at the beginning and the end of the study. Results: The patients’ mean age was 50.91±1.72 years in the intervention group and 51±1.35 in the control group. According to the PG-SGA questionnaire classification, 68.5% of patients had malnutrition at baseline. In the intervention group, the mean score of PG-SGA decreased, which indicated an improvement in patients’ nutritional status. Increased scores in the functional section of QLQC30 and a decrease in the symptom section of this questionnaire indicated the improved quality of life in patients undergoing treatment at the end of the intervention. Albumin (P<0.001) and hemoglobin (P<0.001) levels increased in the intervention group, while there were no significant changes in these variables of the control group. Serum levels of ferritin did not show significant changes in either the intervention or the control group. Conclusion: Identifying nutritional barriers in breast cancer patients and individual diet therapy based on these barriers and nutritional needs reduces nutritional barriers. Consequently, malnutrition would decline, and the quality of life may enhance in these patients.

Combining serum autoantibody measurements with traditional serum biomarkers for the detection of invasive breast cancer.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 13-13
Author(s):  
Meredith C. Henderson ◽  
David Emery Reese ◽  
Sherri Borman ◽  
Susan Yeh ◽  
Alan Hollingsworth
Keyword(s):  
Breast Cancer ◽  
Serum Protein ◽  
Invasive Breast Cancer ◽  
Serum Proteins ◽  
Wide Spectrum ◽  
Great Promise ◽  
Breast Cancer Patients ◽  
Intrinsic Variability ◽  
Protein Biomarkers ◽  
Meso Scale Discovery

13 Background: The use of protein biomarkers for serum-based detection of invasive breast cancer has been problematic due in large part to intrinsic variability in the population as a whole. The Provista Biomarker Assay (PBA) has been shown previously to be highly sensitive across a wide spectrum of clinical signals. The detection of autoantibodies (AAb) holds great promise due to the inherent specificity these biomarkers provide. However, as a clinical-quality diagnostic, it is necessary to utilize a panel comprised of multiple autoantibodies, as individual sensitivity is general low. Our hypothesis was that combining serum protein and autoantibodies together in a panel would result in an increased ability to correctly identify breast cancer. Methods: To maximize clinical performance (sensitivity and specificity), we utilized the Meso Scale Discovery ELISA-based system to measure AAbs from patient sera. We analyzed 134 prospectively collected patient serum samples for a variety of autoantibody targets. These data, together with serum protein biomarker concentrations, produced an analytically robust test that is also highly specific. Results: Consistent with our hypothesis, the inclusion of autoantibodies with serum proteins in the Provista Biomarker Assay improved test specificity above that observed in serum protein biomarkers alone. Individual protein targets had limited ability to differentiate benign conditions from invasive breast cancer. However, factoring in autoantibody values resulted in improved overall accuracy to differentiate serum from benign and invasive breast cancer patients. Conclusions: In the novel approach of combining these two different classes of analytes, we exploit the specificity of AAbs while maintaining high sensitivity through the inclusion of more generalized cancer-associated protein biomarkers. The combination of these two approaches clearly offers unique performance benefits in the early detection of invasive breast cancer that is greater than either component alone.

Immunotoxin and bcl-2 inhibitor combination therapy targeting chondroitin sulfate proteoglycan 4.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 74-74
Author(s):  
Xin Yu ◽  
Stephen T. Keir ◽  
Scott Szafranski ◽  
Steven Clayton ◽  
Ira Pastan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Chondroitin Sulfate ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Chondroitin Sulfate Proteoglycan ◽  
Breast Cancer Cell Lines ◽  
Sulfate Proteoglycan ◽  
Proteoglycan 4 ◽  
Melanoma Cell Lines

74 Background: Immunotoxins (ITs) are a class of bifunctional chimeric proteins composed of an antibody fragment linked to a toxin. When ITs internalize into target cells, they induce protein synthesis inhibition and apoptosis. While ITs are highly specific and potent, the efficacy of IT-based therapies in some tumor cells is limited by hyperactive anti-apoptotic pathways and inefficient translocation of ITs from the endoplasmic reticulum to the cytosol. Therefore, to improve the efficacy of IT-based therapies, we evaluated a dual-pathway therapy that combines an IT with the ABT-737, ABT-263, or ABT-199 small molecule Bcl-2 inhibitor. Methods: The immunotoxin 9.2.27-PE38KDEL (9.2.27-IT) was generated by fusing a truncated mutant form of Pseudomonas exotoxin A to a single-chain variable fragment antibody. It targets human chondroitin sulfate proteoglycan 4 (CSPG4), an antigen highly expressed in a variety of cancer cells. We screened and identified 3 human glioblastoma xenografts, 3 human melanoma cell lines, and 5 human breast cancer cell lines resistant to the 9.2.27-IT despite their high levels of cell surface expression of CSPG4 (IC50 of IT alone was >100 ng/ml in all cell lines except for one melanoma cell line). In vitro cytotoxicity of the 9.2.27-IT —alone or in combination with the individual Bcl-2 inhibitors ABT-737, ABT-263, or ABT199—was assessed. Concentrations of ABT analogues were chosen so that ABT alone did not induce cytotoxicity. Results: The treatment groups that responded to the combination therapy yielded IC50 values ranging from 0.04 – 9 ng/ml for glioblastoma xenografts, 0.21-15 ng/ml for melanoma cell lines, and 4.5-50 ng/ml for breast cancer cell lines. The most potent combination group showed >1000 fold improvement of IC50 compared to using the immunotoxin alone. ABT-737 produced the strongest synergistic effects among the ABT analogues. Preliminary results from in vivo studies further demonstrated that this approach engendered a synergistic response and delayed tumor growth in immunotoxin-resistant mouse tumor models. Conclusions: This new combinatorial approach will potentially help to overcome immunotoxin resistance in cancer patients and provide better therapeutic outcomes.

scholarly journals Serum proteins as tumour markers for breast cancer

1981 ◽  
Vol 43 (4) ◽  
pp. 542-545 ◽  
Author(s):  
P Mattison ◽  
D H Cove ◽  
L Walsh ◽  
A Howell ◽  
B McConkey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Serum Proteins ◽  
Tumour Markers
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