395 research outputs found
In vitro anti-angiogenic properties of LGD1069, a selective retinoid X-receptor agonist through down-regulating Runx2 expression on Human endothelial cells
<p>Abstract</p> <p>Background</p> <p>LGD1069 (Targretin<sup>®</sup>) is a selective retinoid X receptor (RXR) ligand, which is used in patients for cutaneous T-cell lymphoma. Our published study reported that LGD1069 inhibited tumor-induced angiogenesis in non-small cell lung cancer. In present study, we found that LGD1069 suppressed the proliferation, adhesion, invasion and migration of endothelial cells directly, and affected the expression of vegf and some matrix genes.</p> <p>Methods</p> <p>Human umbilical vein endothelial cells (HUVECs) were used for <it>in vitro </it>study. MTT assay and Sulforhodamine B assay were used for cell viability assay; the tube formation assay was used to investigate the effect of LGD1069 on angiogenesis <it>in vitro</it>. <it>In vitro </it>adhesion, migration and invasion of HUVEC cells were analyzed by Matrigel adhesion, migration and invasion assay. Gene expressions were measured by RT-PCR and Western blot analysis.</p> <p>Results</p> <p>Our data showed here that LGD1069 inhibited the activation of TGF-β/Smad pathway significantly. Furthermore, it was demonstrated that expression of Runx2 was suppressed pronouncedly during incubation with LGD1069. Runx2 is a DNA-binding transcription factor which plays a master role in tumor-induced angiogenesis and cancer cells metastasis by interaction with the TGF-β/Smad pathway of transcriptional modulators.</p> <p>Conclusions</p> <p>Our results suggested that LGD1069 may impair angiogenic and metastatic potential induced by tumor cells through suppressing expression of Runx2 directly on human endothelial cells, which may point out new pathway through which LGD1069 display anti-angiogenic properties, and provide new molecular evidence to support LGD1069 as a potent anti-metastatic agent in cancer therapy.</p
A Comparison of Re-sampling Techniques for Pattern Classification in Imbalanced Data-Sets
Class imbalance is a common challenge when dealing with
pattern classification of real-world medical data-sets. An effective countermeasure
typically used is a method known as re-sampling. In this paper
we implement an ANN with different re-sampling techniques to subsequently
compare and evaluate the performances. Re-sampling strategies
included a control, under-sampling, over-sampling, and a combination of
the two. We found that over-sampling and the combination of under- and
over-sampling both led to a significantly superior classifier performance
compared to under-sampling only in correctly predicting labelled classes
Double hadron leptoproduction in the nuclear medium
First measurement of double-hadron production in deep-inelastic scattering
has been measured with the HERMES spectrometer at HERA using a 27.6 GeV
positron beam with deuterium, nitrogen, krypton and xenon targets. The
influence of the nuclear medium on the ratio of double-hadron to single-hadron
yields has been investigated. Nuclear effects are clearly observed but with
substantially smaller magnitude and reduced -dependence compared to
previously measured single-hadron multiplicity ratios. The data are in fair
agreement with models based on partonic or pre-hadronic energy loss, while they
seem to rule out a pure absorptive treatment of the final state interactions.
Thus, the double-hadron ratio provides an additional tool for studying
modifications of hadronization in nuclear matter
Quark helicity distributions in the nucleon for up, down, and strange quarks from semi--inclusive deep--inelastic scattering
Polarized deep--inelastic scattering data on longitudinally polarized
hydrogen and deuterium targets have been used to determine double spin
asymmetries of cross sections. Inclusive and semi--inclusive asymmetries for
the production of positive and negative pions from hydrogen were obtained in a
re--analysis of previously published data. Inclusive and semi--inclusive
asymmetries for the production of negative and positive pions and kaons were
measured on a polarized deuterium target. The separate helicity densities for
the up and down quarks and the anti--up, anti--down, and strange sea quarks
were computed from these asymmetries in a ``leading order'' QCD analysis. The
polarization of the up--quark is positive and that of the down--quark is
negative. All extracted sea quark polarizations are consistent with zero, and
the light quark sea helicity densities are flavor symmetric within the
experimental uncertainties. First and second moments of the extracted quark
helicity densities in the measured range are consistent with fits of inclusive
data
Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction
Evidence for a narrow baryon state is found in quasi-real photoproduction on
a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is
observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1
(syst) MeV. Depending on the background model,the naive statistical
significance of the peak is 4--6 standard deviations and its width may be
somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This
state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s))
pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed
in the pK^+ invariant mass distribution. The absence of such a signal indicates
that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure
Pathological and Biological Differences Between Screen-Detected and Interval Ductal Carcinoma in situ of the Breast
Background: The incidence of ductal carcinoma in situ (DCIS) has risen dramatically with the introduction of screening mammography. The aim was to evaluate differences in pathological and biological characteristics between patients with screen-detected and interval DCIS. Methods: From January 1992 to December 2001, 128 consecutive patients had been treated for pure DCIS at our institute. From these, 102 had been attending the Dutch breast cancer screening program. Sufficient paraffin-embedded tissue was available in 74 out of the 102 cases to evaluate biological marker expression (Her2/neu, ER, PR, p53 and cyclin D1) on tissue microarrays (TMA group). Differences in clinicopathological characteristics and marker expression between screen-detected and interval patients were evaluated. Screen-detected DCIS was classified as DCIS detected by screening mammography, when the two-year earlier examination failed to reveal an abnormality. Interval patients were classified as patients with DCIS detected within the two-year interval between two subsequent screening rounds. Results: Screen-detected DCIS was related with linear branching and coarse granular microcalcifications on mammography (p < .001) and with high-grade DCIS according to the Van Nuys classification (p = .025). In univariate analysis, screen-detected DCIS was related with Her2/neu overexpression (odds ratio [OR] = 6.5; 95%CI 1.3-31.0; p = .020), and interval DCIS was associated with low-grade (Van Nuys, OR = 7.3; 95% CI 1.6-33.3; p = .010) and PR positivity (OR = 0.3; 95%CI 0.1-1.0; p = .042). The multivariate analysis displayed an independent relation of Her2/neu overexpression with screen-detected DCIS (OR = 12.8; 95%CI 1.6-104.0; p = .018). Conclusions: These findings suggest that screen-detected DCIS is biologically more aggressive than interval DCIS and should not be regarded as overdiagnosis
Heart Rate-Corrected QT Interval Helps Predict Mortality after Intentional Organophosphate Poisoning
INTRODUCTION: In this study, we investigated the outcomes for patients with intentional organophosphate poisoning. Previous reports indicate that in contrast to normal heart rate-corrected QT intervals (QTc), QTc prolongation might be indicative of a poor prognosis for patients exposed to organophosphates. METHODS: We analyzed the records of 118 patients who were referred to Chang Gung Memorial Hospital for management of organophosphate poisoning between 2000 and 2011. Patients were grouped according to their initial QTc interval, i.e., normal (<0.44 s) or prolonged (>0.44 s). Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: The incidence of hypotension in patients with prolonged QTc intervals was higher than that in the patients with normal QTc intervals (P = 0.019). By the end of the study, 18 of 118 (15.2%) patients had died, including 3 of 75 (4.0%) patients with normal QTc intervals and 15 of 43 (34.9%) patients with prolonged QTc intervals. Using multivariate-Cox-regression analysis, we found that hypotension (OR = 10.930, 95% CI = 2.961-40.345, P = 0.000), respiratory failure (OR = 4.867, 95% CI = 1.062-22.301, P = 0.042), coma (OR = 3.482, 95% CI = 1.184-10.238, P = 0.023), and QTc prolongation (OR = 7.459, 95% CI = 2.053-27.099, P = 0.002) were significant risk factors for mortality. Furthermore, it was revealed that non-survivors not only had longer QTc interval (503.00±41.56 versus 432.71±51.21 ms, P = 0.002), but also suffered higher incidences of hypotension (83.3 versus 12.0%, P = 0.000), shortness of breath (64 versus 94.4%, P = 0.010), bronchorrhea (55 versus 94.4%, P = 0.002), bronchospasm (50.0 versus 94.4%, P = 0.000), respiratory failure (94.4 versus 43.0%, P = 0.000) and coma (66.7 versus 11.0%, P = 0.000) than survivors. Finally, Kaplan-Meier analysis demonstrated that cumulative mortality was higher among patients with prolonged QTc intervals than among those with normal QTc intervals (Log-rank test, Chi-square test = 20.36, P<0.001). CONCLUSIONS: QTc interval helps predict mortality after intentional organophosphate poisoning
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