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1.
Curr Opin Oncol ; 32(1): 68-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31714259

RESUMO

PURPOSE OF REVIEW: The objective of this review is to discuss the strength and limitations of tissue and liquid biopsy and functional imaging to capture spatial and temporal tumor heterogeneity either alone or as part of a diagnostic framework in non-small cell lung cancer (NSCLC). RECENT FINDINGS: NSCLC displays genetic and phenotypic heterogeneity - a detailed knowledge of which is crucial to personalize treatment. Tissue biopsy often lacks spatial and temporal resolution. Thus, NSCLC needs to be characterized by complementary diagnostic methods to resolve heterogeneity. Liquid biopsy offers detection of tumor biomarkers and for example, the classification and monitoring of EGFR mutations in NSCLC. It allows repeated sampling, and therefore, appears promising to address temporal aspects of tumor heterogeneity. Functional imaging methods and emerging image analytic tools, such as radiomics capture temporal and spatial heterogeneity. Further standardization of radiomics is required to allow introduction into clinical routine. SUMMARY: To augment the potential of precision therapy, improved diagnostic characterization of tumors is pivotal. We suggest a comprehensive diagnostic framework combining tissue and liquid biopsy and functional imaging to address the known aspects of spatial and temporal tumor heterogeneity on the example of NSCLC. We envision how this framework might be implemented in clinical practice.

2.
J Nanosci Nanotechnol ; 20(2): 701-708, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383065

RESUMO

In the present study we developed novel luminescent magnetic nanocomposites termed Fe3O4@polyaniline/carbon dots. First, Fe3O4 magnetic nanoparticles were prepared by the coprecipitation method. The nanoparticles were then coated with polyaniline using the in situ growth method to form Fe3O4@polyaniline nanohybrids, which were endowed with amino functional groups on the surface and avoided the aggregation of Fe3O4 nanoparticles. The X-ray diffraction pattern demonstrated that the crystalline phase of the Fe3O4 nanoparticles was an inverse spinel structure and was not changed in the Fe3O4@polyaniline nanohybrids. The saturation magnetization and the coercive force of the as-prepared Fe3O4@polyaniline nanohybrids measured by a vibrating sample magnetizer were 63.7 emu·g-1 and zero respectively, which indicated that the Fe3O4@polyaniline nanohybrids exhibited excellent superparamagnetism. The Fe3O4@polyaniline nanohybrids were conjugated with carbon dots, prepared from orange juice, via the amide bond between the amino groups on the surface of the Fe3O4@polyaniline nanohybrids and the carboxyl groups on the surface of carbon dots. The obtained luminescent magnetic nanocomposites Fe3O4@polyaniline/carbon dots showed good photoluminescent properties, which hinted that the nanocomposites have potential in drug tracing and magnetic targeted drug delivery. Finally, the anticancer drug methotrexate was loaded into the Fe3O4@polyaniline/carbon dots nanocomposites, forming a novel magnetic targeted drug delivery system. The results confirmed that the novel drug delivery system exhibited excellent drug-loading capability for methotrexate of ca. 70%, and emits strong fluorescence at the wavelength of 360 nm. An in vitro release experiment of the drug delivery system indicated that the cumulative release percentage of methotrexate was 17.2% in the phosphate-buffered saline (pH = 7.4) within 36 h.

3.
J Cell Physiol ; 235(2): 1689-1699, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31298420

RESUMO

Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty-eight patients who had undergone hepatic resection for HCCs were recruited. Paired non-tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with ß-catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.

4.
Neuroimage Clin ; 24: 102098, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31795054

RESUMO

INTRODUCTION: Disruption to white matter pathways is an important contributor to the pathogenesis of Parkinson's disease. Fixel-based analysis has recently emerged as a useful fiber-specific tool for examining white matter structure. In this longitudinal study, we used Fixel-based analysis to investigate white matter changes occurring over time in patients with Parkinson's disease. METHODS: Fifty patients with idiopathic Parkinson's disease (27 men and 23 women; mean age: 61.8 ± 6.1 years), were enrolled. Diffusion-weighted imaging and clinical examinations were performed at three different time points (baseline, first follow-up [after a mean of 24±2 months], and second follow-up [after a mean of 40 ± 3 months]). Additional 76 healthy control subjects (38 men and 38 women; mean age: 62.3 ± 5.5 years) were examined at baseline. The following fixel-based metrics were obtained: fiber density (FD), fiber bundle cross-section (FC), and a combined measure of both (FDC). Paired comparisons of metrics between three different time points were performed in patients. Linear regression was implemented between longitudinal changes of fixel-based metrics and the corresponding modifications in clinical parameters. A family-wise error corrected p < 0.05 was considered statistically significant. RESULTS AND DISCUSSIONS: Early degeneration in the splenium of corpus callosum was identified as a typical alteration of Parkinson's disease over time. At follow-up, we observed significant FDC reductions compared with baseline in white matter, noticeably in corpus callosum; tapetum; cingulum, posterior thalamic radiation, corona radiata, and sagittal stratum. We also identified significant FC decreases that reflected damage to white matter structures involved in Parkinson's disease -related pathways. Fixel-based metrics were found to relate with a deterioration of 39-item Parkinson's Disease Questionnaire, Unified Parkinson's Disease Rating Scale and activity of daily living. A Parkinson's disease -facilitated aging effect was observed in terms of white matter disruption. CONCLUSION: This study provides a thorough fixel-based profile of longitudinal white matter alterations occurring in patients with Parkinson's disease and new evidence of FC as an important role in white matter degeneration in this setting.

5.
PLoS One ; 14(12): e0225792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800606

RESUMO

BACKGROUND: ABO blood group has been associated with cardiovascular disease and cancer. However, whether ABO blood group is associated with nonalcoholic fatty liver disease (NAFLD) remains unknown. The present study aimed to clarify this issue. METHODS: A hospital-based case-control study was performed in southwestern China. A total of 583 newly ultrasound-diagnosed NAFLD cases and 2068 controls were included. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of developing NAFLD were calculated by multivariate logistic regression. A propensity score was developed for adjustment and matching. RESULTS: The proportions of blood groups A, B, AB and O were 31%, 26%, 8% and 35%, respectively. Non-O blood groups were found to be significantly associated with an increased risk of NAFLD (the fully adjusted OR = 1.51, 95% CI: 1.19, 1.91); moreover, compared with blood group O, the fully adjusted ORs of developing NAFLD were 1.50 (95% CI: 1.13, 1.99) for blood group A, 1.59 (95% CI: 1.19, 2.14) for blood group B, and 1.37 (95% CI: 0.86, 2.18) for blood group AB. Similar results were obtained in both propensity-score-adjusted and propensity-score-matched analyses. No evidence of significant effect modification for the association of ABO blood group with the risk of NAFLD was found (all Pinteraction>0.05). CONCLUSIONS: Non-O blood groups are significantly associated with an increased risk of NAFLD. Our findings provide some epidemiological evidence for a possible role of ABO glycosyltransferase in the pathogenesis of NAFLD. However, these findings need to be validated by future studies.

6.
J Agric Food Chem ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789029

RESUMO

ABSTRACT: Debate on the hazard of advanced glycation end products (AGEs) in food has continued for many years, due to their uncertain bioavailability and ability to bind to their receptors (RAGEs) in vivo. There are increasing evidences that free and bound AGEs have many differences in gastrointestinal digestion, intestinal absorption, binding with RAGEs, in vivo circulation and renal clearance. Therefore, this paper compares these aspects between free and bound AGEs by summarizing the available knowledge. Based on the current knowledge, we conclude that it is time to differentiate free AGEs from bound AGEs in food in future studies, since they vary in many aspects that are closely related to their influence on human health. Several perspectives were proposed at the end of this review for further exploring the difference between free and bound AGEs in food.

7.
Biomed J ; 42(5): 352-357, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31783996

RESUMO

BACKGROUND: Severe headaches, projectile vomiting, focal neurological deficits and early onset seizure are regarded as early warning symptoms of subarachnoid hemorrhage (SAH). Earlier diagnosis based on such warning symptoms theoretically would improve the clinical prognosis. However, it is still not clear whether the prognosis is correlated with early warning symptoms. Here, we reviewed warning symptoms and other predictive factors in the emergency room (ER) setting and examined their correlations with mortality. METHODS: Ninety saccular aneurysmal SAH cases were reviewed in a single medical center between January 2011 and December 2013. We examined differences in mortality rate related to warning symptoms, SAH scales, onset-to-ER time, hydrocephalus, and aneurysm size, location, and complexity. Logistic regression analyses were performed to determine the correlations of warning symptoms and other predictive factors with mortality. Receiver operating characteristic (ROC) curve analysis was used to calculate the area the under curve (AUC) of SAH mortality prediction tools. RESULTS: Warning headache, projectile vomiting, the Hunt and Hess scale, Fisher scale, World Federation of Neurological Surgeons (WFNS) grading scale, and modified WFNS (m-WFNS) scale, body mass index, aneurysm complexity and hydrocephalus were significantly different between the survivors and the decedents. The warning headache and WFNS grade were strongly correlated with mortality. The rate of prognostic prediction improved from 90.4% to 94.6% when warning headache was additionally evaluated. CONCLUSIONS: With growing healthcare costs and recognition of the value of palliative care, early identification via warning headache and a detailed clinical history review is necessary for cases of aSAH.

8.
World Neurosurg ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31790836

RESUMO

BACKGROUND: Proximal anterior cerebral (A1) aneurysms are rare among all intracranial aneurysms and are regarded as difficult to treat endovascularly. Treatment is even more challenging in patients with ruptured aneurysms and acute subarachnoid hemorrhage (SAH) condition due to the small size and proximity to perforators. Though challenging, endovascular treatment can provide favorable outcome in such patients. We report our case series of endovascular treatment in ruptured proximal A1 aneurysms. METHODS: Between January 2010 and December 2017, 1,200 aneurysms were treated using endovascular treatment at our center. Fifteen patients with 15 ruptured proximal A1 aneurysms presented with SAH. Five patients underwent simple coiling, 9 underwent balloon assisted coiling, and 1 underwent catheter protective coiling. Medical records and angiographic results were obtained retrospectively. RESULTS: All aneurysms were successfully treated with endovascular treatment. Multiplicity rate was 53.3% (n=8). Initial complete obliteration rate was 93.3% (n=14), with a 13.3% recurrence rate (n=2). One patient suffered from procedure-related complications, specifically, intraoperative bleeding. Eleven patients (73.3%) had good clinical outcome. When excluding Hunt and Hess grade 4 patients, the good outcome rate was 81.8%. CONCLUSIONS: Ruptured proximal A1 aneurysm is a rare condition and is highly associated with multiple aneurysms. Despite being a more difficult and complicated technique, endovascular coiling performed in high-volume, experienced medical centers is still an effective modality with excellent clinical outcome.

9.
Thorac Cancer ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794146

RESUMO

BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and unique subtype of lung cancer. However, the prevalence of driver alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, and the response of tyrosine kinase inhibitor (TKIs) in PLELC has not been thoroughly investigated. METHOD: We retrospectively reviewed the genetic profiles and treatment course of 330 PLELC patients at the Guangdong Lung Cancer Institute (GLCI) from 1st January, 2008 to 30th December, 2018. We searched and analyzed related literature published in PubMed and Web of Science from 1st January, 2000 and 31th August, 2019 based on their mention of "driver mutations" and "the response of TKIs to mutant PLELC". RESULTS: Genetic alterations of EGFR/ALK were tested in 203 patients (203/330, 61.5%). Five patients (5/175, 2.9%) had EGFR mutation and three patients (3/140, 2.1%) had ALK alteration. From the total of 15 articles identified from electronic searches, 1071 PLELC cases mentioned the driver mutations. EGFR mutation and ALK rearrangement were detected in 15 patients and one patient, respectively. In total, there were four EGFR/ALK mutant PLELC patients who received targeted therapy as palliative treatment at the GLCI and in the literature. However, there was disease progression in all cases one month after use of TKIs. CONCLUSION: The mutation rates of EGFR and ALK were low in PLELC. EGFR and ALK TKIs showed limited response in EGFR/ALK mutant PLELC. Further studies are needed to explore other molecular targets to optimize the therapeutic strategy for PLELC.

10.
Medicine (Baltimore) ; 98(49): e18068, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804314

RESUMO

BACKGROUND: Surgical-site infections after primary total joint arthroplasty (TJA) are a significant issue. Antibiotic-impregnated bone cement (AIBC) has been widely used for the treatment of infected joints, but routine use of AIBC in primary TJA remains controversial. In this systematic review, we evaluated the efficacy of AIBC in reducing surgical-site infections after primary TJA. METHODS: We systematically searched Pubmed, EMbase, Cochrane Library, CMB, CNKI, and WanFang Data for studies (published until June 1, 2019) evaluating AIBC use in reducing infection rates. Two reviewers independently screened the literature according to inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Meta-analysis was performed using Review Manager 5.3 software. The registration number is CRD42017078341 in PROSPERO. RESULTS: In total, 10 studies were included, resulting in a sample size of 13,909 arthroplasty cases. The overall pooled data demonstrated that, compared with systemic antibiotics, AIBC was more effective in decreasing deep infection rates (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.14-0.89, P = .030), although there were higher superficial infection rates with AIBC (OR = 1.53, 95% CI = 1.11-2.11, P = .010). Compared to systemic antibiotics alone, AIBC with systemic antibiotics significantly decreased deep infection rates (OR = 0.55, 95% CI = 0.41-0.75, P = .0001) but there was no difference in superficial infection rates (OR = 1.43, 95% CI = 0.81-2.54, P = .220). In the subgroup analysis, both randomized controlled trials and cohort studies had reduced deep infection rates after primary TJA (OR = 0.61, 95% CI = 0.37-0.99, P = .050 and OR = 0.49, 95% CI = 0.34-0.70, P = .0001, respectively). AIBC decreased deep infection rates in both total hip and knee arthroplasty (OR = 0.25, 95% CI = 0.12-0.52, P = .0002 and OR = 0.62, 95% CI = 0.45-0.87, P = .005, respectively). Deep infection rates were significantly decreased by AIBC with gentamicin (OR = 0.31, 95% CI = 0.20-0.49, P < .00001) but unaffected by AIBC with cefuroxime (OR = 0.35, 95% CI = 0.10-1.20, P = .100). Deep infection rates in the AIBC and control groups were similar when laminar airflow was applied to the operating room (OR = 0.90, 95% CI = 0.60-1.35, P = .620); however, without laminar airflow, the efficacy of AIBC in decreasing deep infection rates was significantly higher than that of control group (OR = 0.21, 95% CI = 0.08-0.59, P = .003). CONCLUSIONS: AIBC may significantly decrease deep infection rates after primary total hip and knee arthroplasty, with or without systemic antibiotics.

11.
Biomarkers ; : 1-6, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31762333

RESUMO

Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term exposure at low dose has been seldom studied yet. The current study investigates the time-course change of the metabolomic profiles of urine following the low level long-term exposure of permethrin and identified biomarkers of the chronic toxicity of permethrin.Methods: Male Wistar rats were administrated orally with permethrin (75 mg/kg body weight/day, 1/20 LD50) daily for consecutive 90 days. The urine samples from day 30, day 60, and day 90 after the first dosing were collected and analysed by 1H NMR spectrometry. Serum biochemical analysis was also carried out.Results: Permethrin caused significant changes in the urine metabolites such as taurine, creatinine, acetate, lactate, dimethylamine, dimethylglycine, and trimethylamine-N-oxide. These biological markers indicated prominent kidney and liver toxicity induced by permethrin. However, there was no change in serum biochemical parameters for the toxicity, indicating that metabolomic approach was much more sensitive in detecting the chronic toxicity.Conclusion: The time-course alteration of metabolomic profiles of the urine based on 1H NMR reflects the progressive development of the chronic toxicity with the long-term low-level exposure of permethrin.

12.
Lung Cancer ; 139: 118-123, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31775086

RESUMO

OBJECTIVES: The 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. MATERIALS AND METHODS: Data from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. RESULTS: Expression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients' prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). CONCLUSION: The SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.

13.
Mol Ther Nucleic Acids ; 18: 991-998, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31778957

RESUMO

Galectin-1 (Gal-1) is a pleiotropic homodimeric ß-galactoside-binding protein with a single carbohydrate recognition domain. It has been implicated in several biological processes that are important during tumor progression. Several lines of evidence have indicated that Gal-1 is involved in cancer immune escape and induces T cell apoptosis. These observations all emphasized Gal-1 as a novel target for cancer immunotherapy. Here, we developed a novel Gal-1-targeting DNA aptamer (AP-74 M-545) and demonstrated its antitumor effect by restoring immune function. AP-74 M-545 binds to Gal-1 with high affinity. AP-74 M-545 targets tumors in murine tumor models but suppresses tumor growth only in immunocompetent C57BL/6 mice, not in immunocompromised non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Immunohistochemistry revealed increased CD4+ and CD8+ T cells in AP-74 M-545-treated tumor tissues. AP-74 M-545 suppresses T cell apoptosis by blocking the binding of Gal-1 to CD45, the main receptor and apoptosis mediator of Gal-1 on T cells. Collectively, our data suggest that the Gal-1 aptamer suppresses tumor growth by blocking the interaction between Gal-1 and CD45 to rescue T cells from apoptosis and restores T cell-mediated immunity. These results indicate that AP-74 M-545 may be a potential strategy for cancer immunotherapy.

14.
Opt Express ; 27(21): 30280-30286, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684277

RESUMO

Double optical gating (DOG) technique was implemented with a two-cycle, 1.7 µm driving field to generate isolated attosecond pulses in the 100-250 eV spectrum range. The strong ellipticity dependency of the high harmonics from the 1.7 µm driving field makes polarization based gating method very efficient. When a second harmonic (SH) field is introduced, complete gating can be achieved with less ionization from the leading edge of the driving field, which yields supercontinua with a pulse energy of 0.3 nJ. We perform an attosecond streaking measurement to confirm the generation of isolated attosecond pulses.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31668806

RESUMO

Tripartite motif (TRIM)-containing protein 14 (TRIM14) is implicated in many malignancies. Presently, we studied whether TRIM14 played a role in human papillary thyroid carcinoma (PTC). Herein, TRIM14 was up-regulated in tumor tissues when compared with normal thyroid samples. Among PTC patients, enhanced TRIM14 predicted short recurrence free survival (RFS) time. Then, we found that knockdown of TRIM14 in human PTC K1 cells inhibited cell proliferation, induced cell apoptosis and prevented the tumorigenicity in nude mice. On the contrary, TRIM14 overexpression in human PTC TPC1 cells promoted cell proliferation while inhibited cell apoptosis. TRIM14 exerted its oncogenic activities via promoting the activation of signal transducer and activator of transcription 3 (STAT3). Further, TRIM14 interacted with the suppressor of cytokine-signaling-1 (SOCS1), a negative regulator of STAT3 activation, and knockdown of TRIM14 inhibited SOCS1 ubiquitination. In conclusion, TRIM14 may be a prognostic factor and oncogene in PTC, and may be a potential target for PTC intervention.

16.
Cancer Med ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670906

RESUMO

BACKGROUND: Cervical cancer is one of the most common causes of cancer-associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. METHODS: Western blot was applied to determine the expression of FEN1- and apoptosis-related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. RESULTS: Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. CONCLUSION: FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell.

17.
Int J Med Inform ; 133: 104027, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31706231

RESUMO

AIM: This study aimed to determine the impact of alert frequency and relevance on alert dwell time. METHOD: A 2 × 3 design was used where 127 university students completed 60 prescribing tasks and were presented with a variable frequency of computerized alerts (low, medium and high) with variable relevance (low and high). Participants were instructed to override an alert if it was not relevant to their prescription, and to cancel the order if the alert signalled an error in their order. RESULTS: Participants presented with a small number of alerts spent more time attending to alert content than participants presented with a medium or high number of alerts (respectively median 15.6 s vs 10.8 vs 10.2 s). Alert relevance had no impact on alert dwell time. Alerts requiring an override response were 4.5 times more likely to be correctly actioned than alerts requiring the order to be cancelled. DISCUSSION: Dwell time was influenced by alert frequency, with greater exposure to alerts associated with shorter dwell times. We hypothesize that this was because participants came to learn that spending time on alert information was unnecessary. We propose that when users experience no consequences or feedback from overriding alerts they quickly learn that this action is more efficient and so more rewarding than taking any other action.

18.
FASEB J ; 33(12): 14171-14184, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31725331

RESUMO

Glioblastoma multiforme (GBM) is the most frequently occurring and gravest primary tumor of the CNS in adults. The development of chemoresistance to temozolomide (TMZ), the first-line chemotherapy for GBM, is an important factor contributing to poor treatment outcomes. Down-regulation of O-6-methylguanine-DNA methyltransferase (MGMT) expression in GBM cells is an attractive strategy for overcoming TMZ resistance and improving outcomes. This study revealed that the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) exerts antitumorigenic effects on TMZ-sensitive and TMZ-resistant (TMZ-R) glioma cells. Pretreatment with SNAP not only induced apoptosis, mitochondrial dysfunction, and hypoxia-inducing factor 1, but also resensitized TMZ-R GBM cells to TMZ through down-regulation of MGMT expression. SNAP acted principally through post-translational modification of p53, phosphorylated N-myc downstream regulated gene 1, and MGMT protein stability in TMZ-R GBM cells. Additionally, when applied together, SNAP and TMZ enhanced the inhibition of tumor growth in vitro and in vivo. This study sheds new light on a potential strategy to overcome TMZ resistance in GBM and thus possesses the potential for prolonging survival of patients with GBM.-Tsai, C.-K., Huang, L.-C., Wu, Y.-P., Kan, I.-Y., Hueng, D.-Y. SNAP reverses temozolomide resistance in human glioblastoma multiforme cells through down-regulation of MGMT.

19.
Sci Rep ; 9(1): 16989, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740703

RESUMO

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

20.
Acad Radiol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31761665

RESUMO

RATIONALE AND OBJECTIVES: Radiomic analysis of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images enables the extraction of quantitative information of intratumour heterogeneity. This study investigated whether the baseline 18F-FDG PET/CT radiomics can predict treatment response and survival outcomes in patients with Hodgkin lymphoma (HL). MATERIALS AND METHODS: Thirty-five patients diagnosed with HL who underwent 18F-FDG PET/CT scans before and during chemotherapy were retrospectively enrolled in this investigation. For each patient, we extracted 709 radiomic features from pretreatment PET/CT images. Clinical variables (age, gender, B symptoms, bulky tumor, and disease stage) and radiomic signatures (intensity, texture, and wavelet) were analyzed according to response to therapy, progression-free survival (PFS), and overall survival (OS). Receiver operating characteristic curve, logistic regression, and Cox proportional hazards model were used to examine potential predictive and prognostic factors. RESULTS: High-intensity run emphasis (HIR) of PET and run-length nonuniformity (RLNU) of CT extracted from gray-level run-length matrix (GLRM) in high-frequency wavelets were independent predictive factors for the treatment response (odds ratio [OR] = 36.4, p = 0.014; OR = 30.4, p = 0.020). Intensity nonuniformity (INU) of PET and wavelet short run emphasis (SRE) of CT from GLRM and Ann Arbor stage were independently related to PFS (hazard ratio [HR] = 9.29, p = 0.023; HR = 18.40, p = 0.012; HR = 7.46, p = 0.049). Zone-size nonuniformity (ZSNU) of PET from gray-level size zone matrix (GLSZM) was independently associated with OS (HR = 41.02, p = 0.001). Based on these factors, a prognostic stratification model was devised for the risk stratification of patients. The proposed model allowed the identification of four risk groups for PFS and OS (p < 0.001 and p < 0.001). CONCLUSION: HIR_GLRMPET and RLNU_GLRMCT in high-frequency wavelets serve as independent predictive factors for treatment response. ZSNU_GLSZMPET, INU_GLRMPET, and wavelet SRE_GLRMCT serve as independent prognostic factors for survival outcomes. The present study proposes a prognostic stratification model that may be clinically beneficial in guiding risk-adapted treatment strategies for patients with HL.

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