The Monitor of All-sky X-ray Image (MAXI) mission is the first astronomical payload to be installed on the Japanese Experiment Module — Exposed Facility (JEM-EF or Kibo-EF) on the International Space Station. It has two types of X-ray slit cameras with wide FOVs and two kinds of X-ray detectors consisting of gas proportional counters covering the energy range of 2 to 30 keV and X-ray CCDs covering the energy range of 0.5 to 12 keV. MAXI will be more powerful than any previous X-ray All Sky Monitor payloads, being able to monitor hundreds of Active Galactic Nuclei. A realistic simulation under optimal observation conditions suggests that MAXI will provide all-sky images of X-ray sources of $\sim $20 mCrab ($\sim $7 $\times$ 10$^{-10} $erg cm$^{-2} $s$^{-1}$ in the energy band of 2–30 keV) from observations during one ISS orbit (90 min), $\sim $4.5 mCrab for one day, and $\sim $2 mCrab for one week. The final detectability of MAXI could be $\sim $0.2 mCrab for two years, which is comparable to the source confusion limit of the MAXI field of view (FOV). The MAXI objectives are: (1) to alert the community to X-ray novae and transient X-ray sources, (2) to monitor long-term variabilities of X-ray sources, (3) to stimulate multi-wavelength observations of variable objects, (4) to create unbiased X-ray source cataloges, and (5) to observe diffuse cosmic X-ray emissions, especially with better energy resolution for soft X-rays down to 0.5 keV.
The overexpression of reduced expression in immortalized cells (REIC)/Dickkopf-3 (Dkk-3), a tumor suppressor gene, induced apoptosis in human prostatic and testicular cancer cells. The aim of this study is to examine the potential of REIC/Dkk-3 as a therapeutic target against breast cancer. First, the in vitro apoptotic effect of Ad-REIC treatment was investigated in breast cancer cell lines and the adenovirus-mediated overexpression of REIC/Dkk-3 was thus found to lead to apoptotic cell death in a c-Jun-NH 2 -kinase (JNK) phosphorylaion-dependent manner. Moreover, an in vivo apoptotic effect and MCF/Wt tumor growth inhibition were observed in the mouse model after intratumoral Ad-REIC injection. As multidrug resistance (MDR) is a major problem in the chemotherapy of progressive breast cancer, the in vitro effects of Ad-REIC treatment were investigated in terms of the sensitivity of multidrug-resistant MCF7/ADR cells to doxorubicin and of the P-glycoprotein expression. Ad-REIC treatment in MCF7/ADR cells also downregulated P-glycoprotein expresssion through JNK activation, and sensitized its drug resistance against doxorubicin. Therefore, not only apoptosis induction but also the reversal of anticancer drug resistance was achieved using Ad-REIC. We suggest that REIC/Dkk-3 is a novel target for breast cancer treatment and that Ad-REIC might be an attractive agent against drug-resistant cancer in combination with conventional antineoplastic agents.
Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug Administration approval for the treatment of patients with metastatic breast cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour and the patient's prior treatment, but even when patients are selected on the basis of HER2/neu gene amplification, the single-agent response rate ranges from 12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined clinical samples from patients who had been treated with trastuzumab and analysed the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt signalling pathway was observed to be highly active in the drug-resistant cells, and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells, and marked activation of Akt signalling pathway was also recognised. Moreover, immunohistochemical investigation revealed that trastuzumab treatment was remarkably successful in cells with elevated PTEN expression. Along with the immune-system-associated cytotoxic mechanism, several mechanisms have been proposed for the effect of trastuzumab. PTEN activity might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer.
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