Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) has been shown to induce cellular senescence or apoptosis of breast and prostate cancer cell lines in vitro. To examine whether IGFBP-rP1 acts as a tumor-suppressive protein in vivo, we established two model systems. Expression of IGFBP-rP1 in the human bladder carcinoma cell line EJ-1 was blocked by RNA interference. Human colon cancer cell line DLD-1, which did not express endogenous IGFBP-rP1, was transfected with an IGFBP-rP1 expression vector. When injected intraperitoneally or subcutaneously into nude mice, the IGFBP-rP1-expressing EJ-1 and DLD-1 cell lines grew poorly, whereas the IGFBP-rP1 non-producers grew rapidly and produced large tumors. In monolayer culture the IGFBP-rP1 producers and nonproducers grew similarly in each model, whereas in soft agar culture the former produced far less colonies than the latter. The IGFBP-rP1 producers had IGFBP-rP1 bound to the cell surface, and adhered more efficiently to fibronectin and laminin-5 than the respective non-producers. Expression of IGFBP-rP1 did not affect the efficiency of insulin signaling. These results demonstrate that IGFBP-rP1 strongly suppresses tumor growth by an insulin-independent or insulin-like growth factor-independent mechanism. Cell surface IGFBP-rP1 may reduce the anchorage-independent growth ability, leading to the marked loss of tumorigenicity. (Cancer Sci 2007; 98: 1055-1063)

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Objective: Explore the mechanism of CaSR's involvement in bone metastasis in lung adenocarcinoma. Methods: Immunohistochemistry (IHC) was used to detect the expression of calcium-sensing receptor (CaSR) in 120 cases of lung adenocarcinoma with bone metastasis. Stably transfected cell lines with CaSR overexpression and knockdown based on A549 cells were constructed. The expression of CaSR was verified by western blot and qPCR. The proliferation and migration abilities of A549 cells were tested using cholecystokinin-8 (CCK-8) and Transwell assays, respectively. Western blotting was used to detect the expression of matrix metalloproteinases MMP2, MMP9, CaSR, and NF-κB. The supernatant from each cell culture group was collected as a conditional co-culture solution to study the induction of osteoclast precursor cells and osteoblasts. Western blot and qPCR were used to validate the expression of bone matrix degradation-related enzymes cathepsin K and hormone calcitonin receptor (CTR) and osteoblast-induced osteoclast maturation and differentiation enzyme receptor activator of nuclear factor-κB ligand (RANKL), macrophage colony-stimulating factor (M-CSF), osteoprotegerin (OPG), and PTHrP. Immunofluorescent staining was used to detect F-actin ring formation and osteocalcin expression. Western blot results for NF-κB expression identified a regulatory relationship between NF-κB and CaSR. Results: CaSR expression in lung cancer tissues was significantly higher than that in adjacent and normal lung tissues. The expression of CaSR in lung cancer tissues with bone metastasis was higher than that in non-metastatic lung cancer tissues. The proliferation and migration ability of A549 cells increased significantly with overexpressed CaSR. The co-culture solution directly induced osteoclast precursor cells and the expression of bone matrix degradation-related enzymes significantly increased. Osteoblasts were significantly inhibited and osteoblast-induced osteoclast maturation and differentiation enzymes were significantly downregulated. It was found that the expression of NF-κB and PTHrP increased when CaSR was overexpressed. Osteoclast differentiation factor expression was also significantly increased, which directly induces osteoclast differentiation and maturation. These results were reversed when CaSR was knocked down. Liu et al. CaSR Osteoclast Differentiation Bone Metastasis Conclusions: CaSR can positively regulate NF-κB and PTHrP expression in A549 cells with a high metastatic potential, thereby promoting osteoclast differentiation and maturation, and facilitating the occurrence and development of bone metastasis in lung adenocarcinoma.

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In this paper a multi-classifier method for early recognition of handwritten gesture is presented. Unlike the other works which study the early recognition problem related to the time, we propose to make the recognition according to the quantity of incremental drawing of handwritten gestures. We train a segment length based multi-classifier for the task of recognizing the handwritten touch gesture as early as possible. To deal with potential similar parts at the beginning of different gestures, we introduce a reject option to postpone the decision until ambiguity persists. We report results on two freely available datasets: MGSet and ILG. These results demonstrate the improvement we obtained by using the proposed reject option for the early recognition of handwritten gestures.

In the present study, we evaluated the efficacy and safety of epidermal growth factor receptor tyrosine kinases (EGFR-TKIs) combined with or without angiogenesis inhibitors in advanced non-small-cell lung cancer (NSCLC). We searched published randomized controlled trials (RCTs) comparing EGFR-TKIs with and without angiogenesis inhibitors for the treatment of advanced NSCLC. PubMed, EMBASE, PMC, the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) databases were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). In addition, odds ratios (ORs) and corresponding 95% CIs were pooled for objective response rate (ORR) and disease control rate (DCR). Risk ratios (RRs) and corresponding 95% CIs were pooled for risk of adverse events (AEs). EGFR-TKIs combined with angiogenesis inhibitors showed significant improvements in PFS (HR 0.72, 95% CI 0.61-0.84, P <0.0001), ORR (OR 1.51, 95% CI 1.17-1.97, P=0.002) and DCR (OR 1.49, 95% CI 1.24-1.81, P<0.0001) compared with EGFR-TKIs combined with placebo. However, EGFR-TKIs combined with angiogenesis inhibitors failed to improve OS (HR 0.94, 95% CI 0.84-1.05, P = 0.26). In addition, diarrhea, hypertension, thrombocytopenia, neutropenia, fatigue, rash, and dermatitis acneiform were significantly increased in patients treated with angiogenesis inhibitors. Thus, EGFR-TKIs combined with angiogenesis inhibitors were superior to EGFR-TKIs alone in advanced NSCLC due to their effects on PFS, ORR and DCR, but the increased incidence of AEs had an influence on the tolerability of this combination therapy.

Shade is a major problem facing turf managers worldwide. Availability of low-cost devices and methods for quantifying daily light integral (DLI) offer the turf manager the ability to more precisely determine DLI levels in shade, yet minimal DLI requirements for acceptable turf quality (DLI m ) for many commonly used warm-season turf cultivars grown under longer-term chronic shade stress have not been extensively tested. The objectives of this 2-yr field shade study were to (a) determine effects of growth regulator trinexapac-ethyl (TE) and season (summer or fall) on DLI m of nine commercially available bermudagrass (Cynodon spp.) and zoysiagrass (Zoysia spp.) cultivars; (b) determine effects of shade level and TE on summer percent green cover and root growth; and (c) determine effects of shade treatments on soil temperatures across the growing season. Significantly higher DLI m were noted during summer compared to fall for all cultivars in the study. The DLI m were generally higher for bermudagrass than zoysiagrass cultivars. 'Tifway' required the highest DLI m (ranging from 23.5 to 27.2 mol m −2 d −1 ) of the bermudagrasses. 'TifGrand', 'Celebration', and 'Latitude 36' showed comparable DLI m during summer and fall. Fewer consistent differences were detected between zoysiagrasses, with 'Zorro' and 'Zeon' showing the lowest summer DLI m (18.1 and 19.1 mol m −2 d −1 , respectively) and 'Geo' showing the lowest fall DLI m (11.7 mol m −2 d −1 ). Trinexapac-ethyl reduced DLI m only in Zorro, 'Palisades', and 'JaMur' zoysiagrass, but had no effect on bermudagrass DLI m . The DLI m for a number of cultivars were higher than those previously reported in the literature, which may be attributed to lower mowing heights and/or use of permanent shade structures that were not removed for the duration of the 27-mo study. The findings should benefit turf managers by guiding data-driven, seasonalbased, warm-season turfgrass cultivar selection for shaded environments.

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