Breast--Cancer--Treatment

The goal of our research was to find a cancer treatment that was both effective and cancer specific, sparing immune and normal tissues. We evaluated the efficacy of a combinatorial treatment using the glycolytic inhibitor 3-bromopyruvate and the fatty acid metabolism inhibitor fenofibrate in cancer, immune and normal tissue cells lines. Treatment of the human breast cancer MCF-7 with 3-bromopyruvate and fenofibrate resulted in increased cell death and decreased colony formation. In the immune cells known as peripheral blood mononuclear cells our combinatorial treatment displayed less toxicity than the traditional chemotherapy doxorubicin. Our combinatorial treatment displayed greater toxicity than doxorubicin towards an established breast cell line MCF- 10A, described in the literature as representing normal breast cells. We have shown for the first time a synergistic relationship between 3-bromopyruvate and fenofibrate.

Accelerated Partial Breast Irradiation (APBI) is a common treatment of breast cancer with many modalities including 3D Conformal Radiation Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), and High Dose Rate Brachytherapy (HDR). In this research, a retrospective analysis of patient’s data was performed to analyze the NTCP/TCP (Normal Tissue Complication Probability/Tumor Control Probability) and Dose Volume Histogram (DVH) parameters for HDR with SAVI, 3D, and IMRT and compare them focusing on critical organs such as the heart, ipsilateral lung, chest wall, ribs, and skin. TCP was 90.275%, 55.948%, and 53.369% for HDR, 3D, and IMRT respectively. The ribs were the most sensitive critical organ for all 3 modalities with a mean NTCP of 8%, 15%, and 8% for HDR, 3D, and IMRT respectively. DVH analysis showed HDR spares critical organs more than EBRT except for 2 patients receiving high doses to the ribs and chest wall.

In spite the heavy investments in therapeutic research breast cancer still impacts the
lives of women globally. The projected incidence of new cases in USA for 2008 is 67,770,
with estimated 40,480 deaths. In this study, we investigated the therapeutic efficacy of
Cytoreg®-genistein combination treatment on MCF-7 human breast cancer cells. MCF-7
cells were treated with genistein and Cytoreg® single and combination treatments for 24-
48hr; and the chemosensitivity assessed using bioassays: Trypan Blue and MTT for cell
viability; Ethidium bromide/Rhodamine 123 to assess apoptosis induction; F AM PolyCaspase
binding assay for mechanism of action. The overall data indicated dose- and timedependent
cell death in the MCF-cells and that apoptosis was the major means of treatmentinduced
growth inhibition. There was evidence of Cytoreg®-induced autophagy in the cells.
The overall findings indicated that genistein-Cytoreg® combination was more efficacious
than either genistein or Cytoreg® alone. Cytoreg® enhanced the phytosensitivity of MCF-7
cells to genistein isoflavone.

Phytochemicals are biologically active secondary plant metabolites that could mimic biological activities. In this study genistein isoflavone, a phytochemical present in soy was investigated to determine its effect on the growth of human breast cancer cell line GI-101 and normal breast epithelial cells in vitro. The cells were exposed to varying concentrations of genistein isoflavone for 24 and 48 hour time periods and the effect was determined using post-treatment assays: MTT and Trypan Blue for cell viability; LDH assay for cytotoxicity; Rhodamine 123/Propidium Iodide and Ethidium Bromide/Acridine Orange assays for treatment-induced apoptosis and FAM Poly caspase assay for mechanism of action. The overall results revealed that genistein inhibited cell growth and proliferation through apoptosis in the cells in both time and dose-dependent manner. Normal breast epithelial cells were not significantly affected by genistein at the corresponding dosages. Based on the results obtained, it was concluded that genistein isoflavone could offer therapeutic efficacy in human breast carcinoma without significantly affecting the normal breast epithelial cells.

The therapeutic potential of pomegranate and genistein on growth inhibition of human breast cancer cells was investigated. Methods. Cells (MCF-7) were initially cultured for 48 hr to achieve 80% confluence; and then exposed to the agents in single and combination treatments. Post-treatment analysis was done by using a series of bioassays, including LDH, MTS, AcrO-EthBr, Annexin-FITC and TUNEL assays for growth inhibition and apoptosis detection; and Caspase-3 and NQO1 for molecular pathways of apoptosis. Results. Pomegranate and genistein showed significant dose- and time-dependent cytotoxic and growth inhibition effects as well as apoptosis induction in MCF-7 cancer cells, with significantly higher ( P < 0.01) effects in the combination treatments than in the single treatments. Both drugs induced apoptosis through a caspase-mediated mechanism and independent of NQO1. Discussion and conclusions. Pomegranate and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis with combination treatment being more efficacious than single treatments.