The combined use of CFDNA concentration and integrity is a candidate for a universal screening test of cancer. Upon setting suitable boundaries for the test it might be applied to identify cancer patients, particularly among subjects with predisposing factors. Being less expensive, CFDNA concentration could be applied for mass screening and for patients with values overlapping those of normal and benign subjects, the use of the more expensive, yet more specific, integrity test is suggested.

Objectives: The study aimed to evaluate the dose delivered to the heart during radiotherapy of left-sided and right-sided breast cancer (BC) patients, correlate the dose and laterality of radiotherapy to the possible cardiac damage and evaluate whether Left-ventricular Ejection Fraction (LVEF), Troponin-I (TnI), Creatinine Kinase (CK), Creatine Kinase-MB Relative Index (CK-MBRI) or Lactic Dehydrogenase (LDH) could be used to detect the possible onset of radiotherapy-related cardiotoxicity. Subjects and methods: 80 females were assigned as; 30 left-sided BC patients, 30 right-sided BC patients and 20 healthy females. Patients were treated by radical mastectomy followed by FAC-based chemotherapy and radiotherapy. CT-based 3D-planning was used to generate cardiac dose-volume histograms to assess mean dose received by the heart. Echocardiography was done to all patients before and 1 year after completing radiotherapy. In serum, TnI and CK-MB concentration and CK and LDH activities were determined before and 1 year after radiotherapy. Results: In left-sided patients, mean dose delivered to the heart was significantly higher in left-sided patients with significant association with total radiotherapy dose in left-but not right-sided patients. LVEF before and after radiotherapy were statistically different only in left-sided patients. LVEF one year after radiotherapy dropped 20% or more (DLVEF) in 6 patients, all were left-sided. Using cutoff values 0.08 ng/mL for TnI and 1.4 for CK-MBRI; 11 left-sided patients had abnormal TnI and CK-MBRI vs 5 right-sided patients, the 6 patients identified with DLVEF ! 20 were all among them. Conclusion: the mean dose delivered to the heart is significantly higher in left-sided patients, and it was correlated to the total radiotherapy dose. One year after radiotherapy, DLVEF is possibly good marker of cardiotoxicity onset, however, the persistent elevation of both TnI and CK-MBRI could identify both patients with cardiotoxicity and patients that are thought to be in subclinical phase of cardiac damage.

No abstract

Targeting the thioredoxin/thioredoxin reductase (Trx/TrxR) system is a promising strategy to overcome cancer resistance to conventional therapy. The present study investigated the effect of curcumin on the Trx/TrxR system either alone or in combination with chemotherapy, or radiotherapy in human MCF-7 breast cancer cells seeded in 2 and 3D culture systems. Cell viability, thioredoxin reductase 1 (TrxR1) activity, and the genetic expression of Trx, TrxR1, Bcl2 and BAX genes were studied. The findings showed that the mode of culture significantly affected the response of cancer cells to different treatment modalities, as well as their gene expression patterns. Curcumin treatment resulted in a reduction of breast cancer cell proliferation and induction of apoptosis, an effect that may be mediated by manipulating Trx system components, mainly Trx expression, and to a lesser extent TrxR1 expression and concentration. Furthermore, curcumin increased the sensitivity of breast cancer cells to chemotherapy and radiotherapy by reducing Trx and TrxR1 expression levels. Thus, curcumin may have a potential role as a dose-modifying agent that can be used either to sensitize resistant cells to therapy or to reduce the dose of these therapeutic agents.

Background: MDR continues to be a major challenge to effective chemotherapeutic interventions against cancer. Defining major factor contributing to MDR and inhibiting their action may thus be used for reversing MDR. Aim: This work aimed to evaluate the role played by MRP-1 and GST-Pi in MDR, and to explore the possible role of indomethacin as an inhibitor of chemotherapy resistance in patients with AML. Subjects and methods: The study included 2 groups, one included 20 healthy volunteers and the second included 50 AML patients. All patients received one cycle of standard induction chemotherapy, then regrouped according to their response to either CR group or unremitted group. Unremitted patients received a second cycle of chemotherapy combined with indomethacin. From each subject a blood sample was drawn before and after the 1st cycle of chemotherapy and after the 2nd cycle. From blood, mononuclear cells were separated, mRNA was extracted, and RT-PCR was carried out to detect GST-Pi and MRP-1 gene expression. Results: GST-Pi expression in CR group was 60% before therapy that significantly decreased to 30% after therapy. While in unremitted group, its expression significantly increased from 30% before to 80% after therapy. GST-Pi positive patients had a significantly lower overall and disease free survival time than GST-Pi negative patients (P = 0.000 and 0.039, respectively). While MRP-1 expression was so low (20%) and remained unchanged after therapy in both groups. MRP-1 expression did not affect overall or disease free survival. Taking indomethacin with 2nd cycle of chemotherapy in unremitted patients resulted in a significant inhibition of GST-Pi expression and a significantly longer overall survival time than those taking 2nd cycle chemotherapy alone (P = 0.034).