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Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mu...
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Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n?=?731), 54 gefitinib studies (n?=?1802) and 20 chemotherapy studies (n?=?984) provided median PFS values for each treatment. The pooled median PFS was: 12.4?months (95% accuracy intervals [AI] 11.6–13.4) for erlotinib-treated patients; 9.4?months (95% AI 9.0–9.8) for gefitinib-treated patients; and 5.6?months (95% AI 5.3–6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P?=?0.000 and P?=?0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy.
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The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding...
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The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair. Copyright ? 2018 by The American Association of Immunologists, Inc.
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Introduction: Chemotherapy and radiation therapy are two mainstream strategies applied in the treatment of cancer that is not operable. Patients with hematological or solid tumor malignancies substantially benefit from chemotherap...
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Introduction: Chemotherapy and radiation therapy are two mainstream strategies applied in the treatment of cancer that is not operable. Patients with hematological or solid tumor malignancies substantially benefit from chemotherapeutic drugs and/or ionizing radiation delivered to the site of malignancy. However, considerable adverse effects, including lung inflammation and fibrosis, are associated with the use of these treatment modalities. Areas covered: As we move toward the era of precision health, we are compelled to understand the molecular basis of chemoradiation-induced pathological lung remodeling and to develop effective treatment strategies that mitigate the development of chronic lung disease (i.e. fibrosis) in cancer patients. The review discusses chemotherapeutic agents that are reported to induce or associate with acute and/or chronic lung injury. Expert commentary: There is a need to molecularly understand how chemotherapeutic drugs induce or associate with respiratory toxicities and whether such characteristics are inherently related to their antitumor effect or are collateral. Once such mechanisms have been identified and/or fully characterized, they may be able to guide disease-management decisions including effective intervention strategies for the adverse effects. In the meantime, radiation oncologists should be judicious on the dose of radiation delivered to the lungs, the volume of lung irradiated, and concurrent use of chemotherapeutic drugs. ? 2018, ? 2018 Informa UK Limited, trading as Taylor & Francis Group.
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Agrobacterium tumefaciens oncogenes cause transformed plant cells to overproduce auxin and cytokinin. Two oncogenes encode enzymes that convert tryptophan to indole-3-acetic acid (auxin): iaaM (tryptophan mono-oxygenase) and iaaH ...
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Agrobacterium tumefaciens oncogenes cause transformed plant cells to overproduce auxin and cytokinin. Two oncogenes encode enzymes that convert tryptophan to indole-3-acetic acid (auxin): iaaM (tryptophan mono-oxygenase) and iaaH (indole-3-acetamide hydrolase). A third oncogene (ipt) encodes AMP isopentenyl transferase, which produces cytokinin (isopentenyl-AMP). Inactivation of ipt and iaaM (or iaaH) abolishes tumorigenesis. Because adequate means do not exist to control crown gall, we created resistant plants by introducing transgenes designed to elicit posttranscriptional gene silencing (PTGS) of iaaM and ipt. Transgenes that elicit silencing trigger sequence-specific destruction of the inducing RNA and messenger RNAs with related sequences. Although PTGS has proven effective against a variety of target genes, we found that a much higher percentage of transgenic lines silenced iaaM than ipt, suggesting that transgene sequences influenced the effectiveness of PTGS. Sequences required for oncogene silencing included a translation start site. A transgene encoding a translatable sense-strand RNA from the 5' end of iaaM silenced the iaaM oncogene, but deletion of the translation start site abolished the ability of the transgene to silence iaaM. Silencing A. tumefaciens T-DNA oncogenes is a new and effective method to produce plants resistant to crown gall disease.
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Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroid...
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Saponins display various biological activities including anti-tumor activity. Recently intensive research has been focused on developing saponins for tumor therapies. The diosgenyl saponin dioscin is one of the most common steroidal saponins and exhibits potent anticancer activity in several human cancer cells through apoptosis-inducing pathways. In this paper, we describe the synthesis of several diosgenyl saponin analogues containing either a 2-amino-2-deoxy-beta-d-glucopyranosyl residue or an alpha-l-rhamnopyranosyl-(1-->4)-2-amino-2-deoxy-beta-d-glucopyranosyl residue with different acyl substituents on the amino group. The cytotoxic activity of these compounds was evaluated in MCF-7 breast cancer cells and HeLa cervical cancer cells. Structure-activity relationship studies show that the disaccharide saponin analogues are in general less active than their corresponding monosaccharide analogues. The incorporation of an aromatic nitro functionality into these saponin analogues does not exhibit significant effect on their cytotoxic activity.
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Aim To assess the potential risk of tuberculosis (TB) in patients treated with anti-tumor necrosis factor-alpha (TNF-α) agents in Asia. Methods Absolute risk increase (ARI) of TB was estimated for three widely used anti-TNF-α th...
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Aim To assess the potential risk of tuberculosis (TB) in patients treated with anti-tumor necrosis factor-alpha (TNF-α) agents in Asia. Methods Absolute risk increase (ARI) of TB was estimated for three widely used anti-TNF-α therapies using published standardized incidence ratios (SIR) from the French Research Axed on Tolerance of bIOtherapies registry and incidence (absolute risk [AR]) of TB in Asia. Assuming an association of increased TB risk with anti-TNF-α therapy and country TB AR (incidence), the ARI of TB by country was calculated by multiplying the SIR of the anti-TNF-α therapy by the country's TB AR. The numbers needed to harm (NNH) for each anti-TNF-α agent and numbers needed to treat (NNT) to reduce one TB event using etanercept therapy instead of adalimumab or infliximab were also calculated for each country. Results The ARI of TB with anti-TNF-α therapies in Asian countries is substantially higher than Western Europe and North America and the difference between etanercept versus the monoclonal antibodies becomes more evident. The NNH for Asian countries ranged from 8 to 163 for adalimumab, 126 to 2646 for etanercept and 12 to 256 for infliximab. The NNT to reduce one TB event using etanercept instead of adalimumab therapy ranged from 8 to 173, and using etanercept instead of infliximab therapy the NNT ranged from 13 to 283. Conclusion Higher numbers of patients are at risk of developing TB with anti-TNF-α therapy in Asia compared with Western Europe and North America. The relative lower risk of TB with etanercept may be particularly relevant for Asia, an endemic area for TB.
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Previously, we proposed using an interpolated average CT (IACT) method for attenuation correction (AC) in positron emission tomography (PET), which is a good, low-dose approximation of cine average CT (CACT) to reduce misalignment...
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Previously, we proposed using an interpolated average CT (IACT) method for attenuation correction (AC) in positron emission tomography (PET), which is a good, low-dose approximation of cine average CT (CACT) to reduce misalignments and improve quantification in PET/CT. This study aims to evaluate the performance of IACT for different motion amplitudes. We used the digital four-dimensional (4-D) extended cardiac-torso phantom (XCAT) to simulate maximum of 2, 3, and 4 cm respiratory motions. The respiratory cycle was divided into 13 phases, with average activity and attenuation maps to represent $^{18}$ F-fluorodeoxyglucose ($^{18}$F-FDG) distributions with average respiratory motions and CACT, respectively. The end-inspiration, end-expiration, and midrespiratory phases of the XCAT attenuation maps represented three different helical CTs (i.e., HCT-1, HCT-5, and HCT-8). The IACTs were generated using: 1) 2 extreme + 11 interpolated phases (IACT$_{rm 2o}$ ); 2) 2 phases right after the extreme phases + 11 interpolated phases (IACT $_{rm 2s}$); 3) 4 original + 9 interpolated phases (IACT$_{rm 4o}$). A spherical lesion with a target-to-background ratio (TBR) of 4:1 and a diameter of 25 mm was placed in the base of right lung. The noise-free and noisy sinograms with attenuation modeling were generated and reconstructed with different noise-free and noisy AC maps (CACT, HCTs, and IACTs) by Software for Tomographic Image Reconstruction, respectively, using ordered subset expectation maximization(OS-EM) with up to 300 updates. Normalized mean-square error, mutual information (MI), TBR, image profile, and noi- e-contrast tradeoff were analyzed. The PET reconstructed images with AC using CACT showed least difference as compared to the original phantom, followed by IACT $_{rm 4o}$, IACT$_{rm 2o}$, IACT$_{rm 2s}$, HCT-5, HCT-8, and HCT-1. Significant artifacts were observed in the reconstructed images using HCTs for AC. The MI differences between IACT $_{rm 2o}$ and IACT$_{rm 4o}$ /CACT were <0.41% and <2.17%, respectively. With a slight misplacement of the two extreme phases, IACT$_{rm 2s}$ was still comparable to IACT $_{rm 2o}$ with MI difference of <2.23%. The IACT is a robust and accurate low-dose alternate to CACT.
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Lesions located in the basal ganglia (BG) are thought to be involved in the fatigue observed in neurological disorders. However, the significance of the location of infarcts in poststroke fatigue (PSF) is unknown. This study exami...
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Lesions located in the basal ganglia (BG) are thought to be involved in the fatigue observed in neurological disorders. However, the significance of the location of infarcts in poststroke fatigue (PSF) is unknown. This study examined the association between BG infarcts and PSF. A total of 334 Chinese patients with acute ischemic stroke consecutively admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. At admission, a host of demographic and clinical characteristics was collected and the number and location of acute infarcts were evaluated with MRI. All participants were assessed for PSF with the fatigue severity scale (FSS) 3 months after their index stroke. PSF was defined as a mean FSS score of 4.0 or more. Depressive symptoms were measured by the geriatric depression scale (GDS). Seventy-eight (23.4%) patients had PSF. In the univariate analysis, the PSF group included more females, had higher GDS scores, and a higher number of acute infarcts, and the PSF patients were more likely to have acute infarcts at the BG. Acute BG infarct remained an independent predictor of PSF in the multivariate analysis. In conclusion, these results suggest that BG infarcts may play a role in the development of PSF.
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Recently, it was shown that a dual- or triple-band patch antenna can be designed by cutting U-slots in the patch of a broadband antenna, and the method was applied to the L-probe fed patch, the M-probe fed patch, coax-fed stacked ...
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Recently, it was shown that a dual- or triple-band patch antenna can be designed by cutting U-slots in the patch of a broadband antenna, and the method was applied to the L-probe fed patch, the M-probe fed patch, coax-fed stacked patches, and aperture coupled stacked patches. All these cases involve either a rather complicated feed, or more than one patch, or more than one layer. In this communication, this method is applied to a broadband U-slot patch antenna. When one additional U-slot patch is cut in the patch, a dual-band antenna results. When two additional U-slot patches are cut in the patch, a triple-band antenna results. The advantages of the resultant configurations are (1) the feed is simple and (2) the structures remain single-layer and single-patch. Both simulation and measurement results are presented to demonstrate the feasibility of this design.
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