An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial.

Effects of phytoestrogens on the activity and growth of primary breast cancer cells ex vivo.

AIM: To explore the ex vivo effects of phytoestrogens on primary human breast cancer cells. METHODS: Breast cancer cells were obtained from patients who underwent primary breast cancer surgery, which were treated with 10-8 M 17ß-estradiol (E2 ), one of three phytoestrogens (genistein, resveratrol and quercetin, 10-7 M), and a combination of E2 and one of the three phytoestrogens for 48 h. These cells were then extracted for viability and apoptosis assay. The proteins involved in the proliferative and apoptotic pathways were evaluated by western blot analysis. RESULTS: Human breast cancer cell viability was inhibited by all phytoestrogens but induced by E2 with or without phytoestrogen. Apoptotic cells, as well as the proteins involved in apoptotic pathway and estrogen receptor (ER) ß, were significantly increased in the cells treated with phytoestrogen alone. The use of E2 with or without a phytoestrogen revealed completely opposite results. The proteins involved in the proliferative pathway and ER α expression were all increased in the cultures with E2 with or without phytoestrogens. CONCLUSION: In the presence of E2 , these phytoestrogens lose the effects of suppressing breast cancer cells; contrastingly, induce growth stimulatory effects by inhibiting apoptosis and stimulating proliferation in primary breast cancer cells. Thus, the effects of phytoestrogens on breast cancer should be considered as E2 still present in breast cancer tissue.

Is Danggui Safe to be Taken by Breast Cancer Patients?-A Skepticism Finally Answered by Comprehensive Preclinical Evidence.

Angelica sinensis (AS, Danggui) has long been regarded to stimulate breast cancer growth; hence, the use of AS in breast cancer patients remains a major concern for both patients and practitioners. Since safety studies of herbs would be unethical to carry out in patients, the present study aimed to investigate the potential unsafe effects of AS in a systematic pre-clinical approach. Human breast cancer cells, breast orthotopic tumor-bearing mouse models, as well as primary breast cancer cells from patients' tumors were used to evaluate the effect of AS hot water extract on the progression of breast tumors and/or growth of breast cancer cells. We showed that AS is not that stimulatory in breast cancer both in vitro and in vivo, though AS should still be used with caution in estrogen receptor-positive breast cancer patients. This novel approach of applying breast cancer cell lines, xenograft, and syngeneic tumors models, as well as primary breast cancer cells from patients' tumors in Chinese medicines safety evaluation was proven feasible. Our finding is important information for patients, Chinese medicine practitioners, and clinicians on the safety use of AS in breast cancer, which will affect future clinical practice.

Radiation Gene-expression Signatures in Primary Breast Cancer Cells.

BACKGROUND/AIM: In breast cancer (BC) care, radiation therapy (RT) is an efficient treatment to control localized tumor. Radiobiological research is needed to understand molecular differences that affect radiosensitivity of different tumor subtypes and the response variability. The aim of this study was to analyze gene expression profiling (GEP) in primary BC cells following irradiation with doses of 9 Gy and 23 Gy delivered by intraoperative electron radiation therapy (IOERT) in order to define gene signatures of response to high doses of ionizing radiation. MATERIALS AND METHODS: We performed GEP by cDNA microarrays and evaluated cell survival after IOERT treatment in primary BC cell cultures. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to validate candidate genes. RESULTS: We showed, for the first time, a 4-gene and a 6-gene signature, as new molecular biomarkers, in two primary BC cell cultures after exposure at 9 Gy and 23 Gy respectively, for which we observed a significantly high survival rate. CONCLUSION: Gene signatures activated by different doses of ionizing radiation may predict response to RT and contribute to defining a personalized biological-driven treatment plan.