Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer-VEGF complex blocking its interaction with VEGF-receptor.

Bovine lactoferrin targets apoptotic and EGFR mechanisms in breast cancer

 This research investigated the anti-cancer effects of milk protein, lactoferrin. It was found that lactoferrin specifically induced cell death in breast cancer cells and was non-toxic to normal mammary gland cells. Key molecular mechanisms targeted by lactoferrin were elucidated in this study which provides important insight into the activity of this protein as an anti-cancer agent.

EpCAM aptamer-mediated survivin silencing sensitized cancer stem cells to doxorubicin in a breast cancer model

Understanding the molecular basis of drug resistance and utilising this information to overcome chemoresistance remains a key challenge in oncology. Here we report that survivin, a key protein implicated in drug resistance, is overexpressed in cancer stem cell pool of doxorubicin-resistant breast cancer cells. Moreover, by utilising an active targeting system consisting of an RNA aptamer targeted against the epithelial cell adhesion molecule and a Dicer substrate survivin siRNA, we could deliver a high dose of the siRNA to cancer stem cells in xenograft tumours. Importantly, silencing of survivin with this aptamer-siRNA chimera in cancer stem cell population led to the reversal of chemoresistance, such that combined treatment with low dose of doxorubicin inhibited stemness, eliminated cancer stem cells via apoptosis, suppressed tumour growth, and prolonged survival in mice bearing chemoresistant tumours. This strategy for in vivo cancer stem cell targeting has wide application for future effective silencing of anti-death genes and in fact any dysregulated genes involved in chemoresistance and tumour relapse.

Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer.

Effectiveness, costs, and cost-effectiveness of recruitment strategies for a mammographic screening program to detect breast cancer

BACKGROUND AND PURPOSE: Since effective and affordable recruitment methods are essential for the widespread implementation of mammographic screening for detection of breast cancer, we studied the effectiveness, the costs, and the cost-effectiveness of various recruitment strategies in the population targeted by a pilot Australian program that offered free mammography screening between 1988 and 1990. METHODS: We evaluated three public recruitment strategies--local newspaper articles, community promotion, and promotion to physicians--and five personal strategies--invitation letters with or without specified appointment times, either alone or with a follow-up letter, or telephone call to nonattenders. The effectiveness of public recruitment strategies was estimated from monthly attendance rates by Poisson regression analysis, while the probability of attendance in response to personal strategies was calculated using logistic regression analysis. Costs were determined by resource usage studies. The cost-effectiveness ratios for personal strategies were determined using decision analysis. RESULTS: The costs in 1988-1989 Australian dollars per woman recruited were $22 for local newspaper articles and $106 for community promotion. No detectable increase in attendance resulted from promotion to physicians. When the cost of reserving an appointment was considered, the most cost-effective personal recruitment strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders. This strategy recruited 35.6% of women in the sample targeted and cost $10.52 per attendee. In comparison, the most effective personal recruitment strategy was a letter with a specified appointment time followed by a second letter to nonattenders, which recruited 44.1% of women at an average cost of $19.99 and a marginal cost of $59.71 per additional attendee. CONCLUSIONS: Personal recruitment strategies were more cost-effective than public strategies. The most cost-effective personal strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders.

Patterns of surgical treatment of breast cancer in Victoria

We analysed data on admissions to Victorian public hospitals for surgical treatment of breast cancer over the period July 1985 to December 1988. Of the 2993 women admitted, 28.7% received breast-preserving surgery. The probability of a woman being treated conservatively was dependent on age, with women aged less than 50 or more than 70 years more likely to receive breast-preserving surgery than women aged 50-69. There was an age-specific change, of marginal statistical significance, in the proportion of women receiving breast-preserving surgery over the period. The public hospitals admissions database is a potentially useful means of monitoring patterns of surgical treatment.