Shortest Path Computation with No Information Leakage

Shortest path computation is one of the most common queries in location-based services (LBSs). Although particularly useful, such queries raise serious privacy concerns. Exposing to a (potentially untrusted) LBS the client's position and her destination may reveal personal information, such as social habits, health condition, shopping preferences, lifestyle choices, etc. The only existing method for privacy-preserving shortest path computation follows the obfuscation paradigm; it prevents the LBS from inferring the source and destination of the query with a probability higher than a threshold. This implies, however, that the LBS still deduces some information (albeit not exact) about the client's location and her destination. In this paper we aim at strong privacy, where the adversary learns nothing about the shortest path query. We achieve this via established private information retrieval techniques, which we treat as black-box building blocks. Experiments on real, large-scale road networks assess the practicality of our schemes.Comment: VLDB201

Detection and tracking of discrete phenomena in sensor-network databases

This paper introduces a framework for Phenomena Detection and Tracking (PDT, for short) in sensor network databases. Examples of detectable phenomena include the propagation over time of a pollution cloud or an oil spill region. We provide a crisp definition of a phenomenon that takes into consideration both the strength and the time span of the phenomenon.We focus on discrete phenomena where sensor readings are drawn from a discrete set of values, e.g., item numbers or pollutant IDs, and we point out how our work can be extended to handle continuous phenomena. The challenge for the proposed PDT framework is to detect as much phenomena as possible, given the large number of sensors, the overall high arrival rates of sensor data, and the limited system resources. Our proposed PDT framework uses continuous SQL queries to detect and track phenomena. Execution of these continuous queries is performed in three phases; the joining phase, the candidate selection phase, and the grouping/output phase. The joining phase employs an in-memory multi-way join algorithm that produces a set of sensor pairs with similar readings. The candidate selection phase filters the output of the joining phase to select candidate join pairs, with enough strength and time span, as specified by the phenomenon definition. The grouping/ output phase constructs the overall phenomenon from the candidate join pairs. We introduce two optimizations to increase the likelihood of phenomena detection while using less system resources. Experimental studies illustrate the performance gains of both the proposed PDT framework and the proposed optimizations

The role of Herceptin in early breast cancer

Herceptin is widely regarded as the most important development in the treatment of breast cancer since Tamoxifen and the development of the multidisciplinary team (MDT). It is particularly exciting from an oncological polint of view as it represents success in the emerging field of specific targeted therapies to specific molecular abnormalities in tumour cells. This review will focus on the nature of the Her2 overexpression and the role of herceptin in the treatment of early breast cancer

Tamoxifen and the Rafoxifene analog LY117018: their effects on arachidonic acid release from cells in culture and on prostaglandin I(2 )production by rat liver cells

BACKGROUND: Tamoxifen is being used successfully to treat breast cancer. However, tamoxifen also increases the risk of developing endometrial cancer in postmenopausal women. Raloxifene also decreases breast cancer in women at high risk and may have a lower risk at developing cancer of the uterus. Tamoxifen has been shown to stimulate arachidonic acid release from rat liver cells. I have postulated that arachidonic acid release from cells may be associated with cancer chemoprevention. METHODS: Rat liver, rat glial, human colon carcinoma and human breast carcinoma cells were labelled with [(3)H] arachidonic acid. The release of the radiolabel from these cells during incubation with tamoxifen and the raloxifene analog LY117018 was measured. The prostaglandin I(2 )produced during incubation of the rat liver cells with μM concentrations of tamoxifen and the raloxifene analog was quantitatively estimated. RESULTS: Tamoxifen is about 5 times more effective than LY117018 at releasing arachidonic acid from all the cells tested. In rat liver cells only tamoxifen stimulates basal prostaglandin I(2 )production and that induced by lactacystin and 12-O-tetradecanoyl-phorbol-13-acetate. LY117018, however, blocks the tamoxifen stimulated prostaglandin production. The stimulated prostaglandin I(2 )production is rapid and not affected either by preincubation of the cells with actinomycin or by incubation with the estrogen antagonist ICI-182,780. CONCLUSIONS: Tamoxifen and the raloxifene analog, LY117018, may prevent estrogen-independent as well as estrogen-dependent breast cancer by stimulating phospholipase activity and initiating arachidonic acid release. The release of arachidonic acid and/or molecular reactions that accompany that release may initiate pathways that prevent tumor growth. Oxygenation of the intracellularly released arachidonic acid and its metabolic products may mediate some of the pharmacological actions of tamoxifen and raloxifene

Altered sirtuin expression is associated with node-positive breast cancer

Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, ‘nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications

Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications.

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics-particularly those targeted to cross the BBB-as well as detection of small nonpermeable metastases

Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer

Background Suppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors. Methods SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period. Results SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression. Conclusion Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer

siRNA inhibition of telomerase enhances the anti-cancer effect of doxorubicin in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells.</p> <p>Methods</p> <p>siRNA targeting the mRNA of the protein component of telomerase, the telomerase reverse transcriptase (hTERT), was transfected into two breast cancer cell lines. The siRNA inhibition was confirmed by RT-PCR and western blot on hTERT mRNA and protein levels, respectively, and by measuring the activity level of telomerase using the TRAP assay. The effect of the hTERT siRNA on the tumorigenicity of the breast cancer cells was also studied <it>in vivo </it>by injection of the siRNA-transfected breast cancer cells into nude mice.</p> <p>The effects on cell viability, apoptosis and senescence of cells treated with hTERT siRNA, doxorubicin, and the combined treatment of doxorubicin and hTERT siRNA, were examined <it>in vitro </it>by MTT assay, FACS and SA-β-galactosidase staining.</p> <p>Results</p> <p>The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. <it>In vivo</it>, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 μM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 μM doxorubicin killed twice as many cancer cells, showing a cumulative effect of the two treatments.</p> <p>Conclusion</p> <p>The study demonstrated the potential of telomerase inhibition as an effective treatment for breast cancer. When used in conjunction to doxorubicin, it could potentiate the cytotoxic effect of the drug to breast cancer cells.</p