- Ex vivo sub-cellular imaging of DNA-damage and -repair in circulating leukocytes
- Homocystein level in blood-plasma
- Pathology-specific protein-profiles in circulating leukocytes
Metabolomics Genomics Proteomics
Breast and Gynecologic Cancers Research
Breast-conserving lumpectomy followed by radiation therapy has been shown to be an alternative strategy, competitive to mastectomy, in preventing mortality caused by breast cancer. However, besides negative short-term effects (blood flow disturbances, painful erythema, etc.) breast irradiation causes severe long-term side-effects (leucopenia, anemia, breast edema, fibrosis, increase of angiosarcoma, leukemia, myelodysplastic syndromes). Therefore, the identification of individual susceptibility to radiation and improved patient-specific radiotherapy planning are highly desirable for personalised treatment in breast cancer.
Why early and predictive diagnosis is crucial for long-term outcomes of breast cancer?
Breast cancer is the most common cause of cancer death among women with an average incidence rate of 10-12 per 100 women. In 2005, breast cancer led to 502,000 deaths worldwide. Advanced stages of breast cancer lead to the development of metastasis predominantly in the lymph nodes, bone, lung, skin, brain, and liver. Although breast-MRI is currently the most sensitive diagnostic tool for breast imaging, its specificity is limited resulting in a negative impact for surgical management in approximately 9 % of cases. Early diagnosis has been demonstrated to be highly beneficial, enabling significantly enhanced therapy efficiency and possibly full recovery.
Some recently developed, advanced diagnostic approaches focus on minimally invasive blood analysis as a valuable source of information concerning individual stress reactions under irradiation treatment. The prognostic role of leukocyte activity in breast cancer patients has long been recognised. Although fluctuating considerably among both node- negative and -positive patients, this activity has been demonstrated to be significantly lower in patients with a greater tumour burden. The authors emphasise the necessity for a more comprehensive analysis that would consider late effects of radiotherapy, stress-response and repair kinetics in terms of diagnostic and prognostic purposes in favour of the personalised treatment of breast cancer patients.
In addition to the increased risk of tumour-spreading by invasive biopsies, a serious disadvantage of utilizing biopsy samples for molecular imaging is the mixed cell population obtained, strongly varying from case to case, and resulting in differential gene expression with limited specificity related to the pathology.
The central concept of our research in favour to non-invasive diagnosis focuses on
1. blood-tests for the prediction of an individual’s predisposition,
2. highly homogeneous subgroups considering single criteria of patients grouping such as age, familial/genetic predisposition, benign breast pathologies versus malignancy, pre/peri/post-menopausal status, accompanying diseases (e.g. metabolic disorder), etc.
3. combined biomarkers to increase the predictive power of the diagnostic approach.
Measurements of Homocysteine in blood-plasma
Measurements of homocysteine in EDTA-plasma were performed using high performance liquid chromatography (HPLC) as described elsewhere.
Comet Assay analysis
The “Comet assay” provides a simple and effective method for evaluation of DNA damage and DNA-repair capacity in single cells such as leukocytes. The principle of the assay is based upon the ability of DNA fragments to migrate out of the cell under the influence of an electric field. An evaluation of the “comet” tail shape and DNA fragments migration pattern allows for assessment of DNA damage and repair capacity.
There are currently no biomarkers annotated for this protocol.
No datasets are currently associated with this protocol.
The New and Continuing EDRN Principal Investigator Orientation will take place October 15–16, 2015 in Bethesda, Maryland.
Thank you to everyone who made the 29th EDRN Steering Committee Meeting a success. The orientation for new and continuing EDRN PIs will be held October 15-16, 2015 on the NCI campus. More information will be available later this summer.