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1.
Mol Cancer ; 19(1): 26, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-32020881

RESUMEN

BACKGROUND: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. METHODS: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. RESULTS: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. CONCLUSION: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

2.
Clin Exp Pediatr ; 2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32024330

RESUMEN

Background: The decision for transannular patching (TAP) during tetralogy of Fallot (TOF) repair depends on pulmonary valve annulus size and the z-score of pulmonary annulus is most commonly used as a predictor. The z-scores showed a weakness that it is ambiguous because of the use of varied z-score data sets. Purpose: This study aimed to identify the echocardiographic and other key factors that warranted a change in the surgical method during TOF surgery. Methods: Sixty two patients were enrolled and divided into a pulmonary valve (PV) preservation group and a TAP group. Their medical records were reviewed. Results: The z-score for PV annulus (PVA), the ratio of the size of PVA to aortic annulus, and the ratio of the size of the PVA and descending aorta (DAO) were significantly different between PV preservation group and TAP group (-1.72±1.52 versus -3.07±1.94, P = 0.004, 0.62±0.12 versus 0.50±0.14, P = 0.002, 1.32±0.32 versus 1.07±0.36 and P = 0.008, respectively). For TAP repair, the PVA z-score was with a sensitivity of 65.4% and a specificity of 73.1%, the ratio of the size of PVA to aortic annulus with a sensitivity of 73.1% and a specificity of 65.4%, the ratio of the size of PVA to DAO with a sensitivity of 69.2% and a specificity of 57.7%. The TAP group showed more monocuspid PV (P = 0.011), and the PV preservation group showed more tricuspid PV (P = 0.027). Commissurotomy was more frequently performed in the PV preservation group than the TAP group (P = 0.001). Of patients with commissurotomy, 58% showed PV z score < -2. Conclusion: Although various echocardiographic parameters may be used as predictors for determining the surgical method for TOF patients, the morphology and tissue characteristics of the PV should be also considered importantly.

3.
Sci Justice ; 60(1): 86-94, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31924293

RESUMEN

Over the past decade, illicit drugs have been founded in marketed products, which pose a risk to public health. In particular, newly designed analogues synthesized by chemical modification of parent compounds to avoid detection by authorities are frequently detected worldwide. Although many analytical methods for determination of drugs have been reported, analytical methods using high-resolution mass spectrometry, which has the advantage of rapid screening and accurate identification of new substances, are necessary to control illicit drugs in marketed products. In this study, a rapid analytical method using an Orbitrap™ mass spectrometer for identification of illicit drugs in marketed products was developed. The 32 drugs were classified as benzodiazepine-, synthetic cannabinoid-, amphetamine- and benzylpiperazine-type drugs according to their chemical structures, and from their fragmentation patterns in tandem mass spectrometry spectra of an established method. The method validation gave a limit of detection of 0.06-5.30 ng/mL and a limit of quantification of 0.18-16.50 ng/mL, high linearity (R2 > 0.994) and mean recoveries of spiked matrix-blank samples ranging from 83.7% to 117.1%. Approximately 71% of 21 samples collected over 3 years were found to individually contain one of four types of benzodiazepines or two different synthetic cannabinoids. In one case, levels as high as 827.2 mg/g were measured suggesting adulteration at high levels, which suggests that potential illicit products containing drugs should be regularly screened to protect public health.

4.
Artículo en Inglés | MEDLINE | ID: mdl-31958310

RESUMEN

OBJECTIVE: To examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM. RESEARCH DESIGN AND METHODS: A total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case-control study. Fasting venous blood samples were collected at the prenatal visit of the first trimester and during OGTT of the second trimester. Plasma concentration of fetuin-A and insulin was determined. RESULTS: The plasma fetuin-A concentration in women with GDM was significantly higher than NGT controls in both the first trimester (medians: 403.0 pg/mL vs 273.4 pg/mL; p<0.05) and the second trimester (medians: 475.7 pg/mL vs 290.8 pg/mL; p<0.05) and notably increased from the first to the second trimester. Multivariate linear regression analysis showed that the change in fetuin-A concentration was associated with the changes in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, and HOMA of ß-cell function (HOMA-ß) (p<0.05). The highest quartile of the increase in fetuin-A concentration from the first to the second trimester was associated with a higher risk of developing GDM compared with the lowest quartile (OR 2.14; 95% CI 1.05 to 4.37). CONCLUSIONS: The dynamic change in fetuin-A levels was associated with the changes in insulin resistance and ß-cell function from the first to the second trimester, and was associated with an increased risk of the development of GDM, indicating that fetuin-A could be a biomarker to predict the risk of GDM. TRIAL REGISTRATION NUMBER: NCT03814395.

5.
Cell Death Dis ; 11(1): 43, 2020 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-31969559

RESUMEN

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain- or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

6.
Mol Cells ; 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31940718

RESUMEN

The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed. We found that the level of collaterals from direct pathway MSNs in the external segment of the globus pallidus (GPe) ('bridging collaterals') was decreased in these mice, and this was accompanied by behavioral inhibition under stress. Furthermore, additional manipulations that could further decrease or restore the level of the bridging collaterals resulted in an increase in behavioral inhibition or active behavior in the G2CT mice, respectively. Collectively, our data indicate that the striatum of the basal ganglia network integrates negative emotions and controls appropriate coping responses in which the bridging collateral connections in the GPe play a critical regulatory role.

7.
Artículo en Inglés | MEDLINE | ID: mdl-31910027

RESUMEN

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance, and patients with GDM have a higher risk of cardiovascular disease. Multiple microRNAs (miRNAs) are reported to be involved in the regulation of myocardial injury. Moreover, miR-873 was predicted to target insulin-like growth factor binding protein 2 (IGFBP2) through bioinformatic analysis, which was further confirmed using a luciferase assay. Thus, our objective was to assess whether microRNA-873 (miR-873) affects insulin resistance and myocardial injury in an established GDM rat model. The GDM rats were treated with miR-875 mimic or inhibitor, or IGFBP2 siRNA. The effects of miR-875 and IGFBP2 on the cardiac function, insulin resistance, and myocardial injury were evaluated by hemodynamic measurements, determination of biochemical indices of myocardium and serum, and insulin homeostatic model assessment. The results indicated that down-regulation of miR-873 up-regulated the expression of IGFBP2 and promoted the activation of PI3K/AKT/mTOR axis. With down-regulation of miR-873 in GDM rats, the cardiac function was improved, and the myocardial apoptosis was inhibited, coupled with elevated activity of superoxide dismutase, carbon monoxide synthase, and the nitric oxide content. Besides, the inhibition of miR-873 in GDM rats modulated the insulin resistance and reduced myocardial apoptosis. Overall, the data showed that inhibition of miR-873, by targeting IGFBP2, may regulate the insulin resistance and curtail myocardial injury in GDM rats through activating PI3K/AKT/mTOR axis, thus providing a potential means of impeding the progression of GDM.

8.
Sci Total Environ ; 709: 136246, 2020 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-31927434

RESUMEN

BACKGROUND: Previous studies examined the associations of particulate matters (PM) with fetal growth in utero or birth weight with inconsistent results, and few studies investigated that whether the associations of PM with fetal growth in utero also present at birth. We aimed to investigate the associations of PM with both fetal growth in utero and birth weight. METHODS: We established a birth cohort (2014-2017) with 18,863 singleton pregnancies in Tongzhou Maternal and Child Hospital of Beijing, China. Maternal exposure to PM with aerodynamic diameters ≤2.5 µm and ≤ 10 µm (PM2.5/PM10) during pregnancy was estimated using the inverse distance weighting method. Estimated birth weight (EFW) was assessed by ultrasound measurements and birth weight was measured at birth, which were both standardized as gestational-age- and gender-adjusted Z-score. EFW undergrowth, low birth weight (LBW) and small-for-gestational-age were defined as the categorized outcomes. Generalized estimating equations and generalized linear regression were used to examine the associations of PM with quantitative and categorized outcomes, controlling for temperature, greenspace and individual covariates. RESULTS: A 10 µg/m3 increase in PM2.5 and PM10 were associated with lower EFW Z-score [-0.031, 95% confident interval (CI): -0.047, -0.016 and -0.030, 95% CI: -0.043, -0.017]. A 10 µg/m3 increase in PM2.5 was associated with lower birth weight Z-score (-0.035, 95% CI: -0.061, -0.010) and higher risk of LBW (OR = 1.240, 95% CI: 1.019, 1.508). These results remained robust in co-pollutant models and sensitivity analyses. We didn't find significant results in other analyses. CONCLUSIONS: The study identified an inverse association between PM and fetal growth in utero. The association between PM2.5 and fetal growth persisted from pregnancy to birth. This study supported that further actions towards controlling air pollution are strongly recommended for promoting early-life health.

9.
Biochem Biophys Res Commun ; 522(3): 731-735, 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-31791585

RESUMEN

Rheumatoid arthritis (RA) is a highly inflammatory autoimmune disease. Although proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-6, play a key role in the pathogenesis of RA, the causes of chronic inflammation are not fully understood. Here, we report that protein phosphatase magnesium-dependent 1A (PPM1A) levels were increased in RA synovial fluid compared with osteoarthritis (OA) synovial fluid and positively correlated with TNF levels. In addition, PPM1A expression was increased in synovial tissue from RA patients and joint tissue from a mouse model of arthritis. Finally, extracellular PPM1A induced inflammation by stimulating macrophages to produce TNF through toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) signaling pathway. Our findings suggest that extracellular PPM1A may contribute to the pathogenesis of RA by functioning as a damage-associated molecular pattern (DAMP) to induce inflammation.

10.
Int J Rheum Dis ; 23(1): 92-100, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31802639

RESUMEN

AIMS: To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. METHODS: We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. RESULTS: Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83 months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR] = 7.19, P = .001), pleuritis and/or pericarditis (HR = 3.28, P = .012), childhood-onset (HR = 3.57, P = .012), and late-onset (HR = 4.65, P = .011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. CONCLUSION: This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.

11.
ACS Appl Mater Interfaces ; 12(2): 2926-2934, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31750647

RESUMEN

Covalent organic frameworks (COFs) have been widely used in catalysis, energy storage, environmental protection, and separation. However, they require a long assembly period (∼3 days) and complex synthesis conditions; differences in water resistance have restricted their overall versatility. In this paper, the preparation of COF-DhaTab was optimized, and this process can be easily performed in air. Thus, it is feasible for the scale-up of COF-DhaTab in the near future. The superhydrophobic properties of COF-DhaTab (water contact angle, >150°) can be created by regulating the wettability of COF-DhaTab by grafting fluoride. When the grafting degree of fluoride increased to 4.32%, the water contact angle of COFs increased from 0° to more than 150°. The grafted COFs are termed COF-DhaTab fluoride (COF-DTF). The chemically modified COF-DhaTab maintains its original porosity and crystallinity. The superhydrophobic COF-DTF can be applied to various substrates, for example, foam, fabric, and glass. These all exhibit outstanding water repellency, self-healing, and excellent self-cleaning. Importantly, the coating maintains its original superhydrophobicity even under extremely acidic/basic conditions (pH = 1-14) and toward boiling water (100 °C). Furthermore, COF-DTF displays long-term stability and is easily scaled. It is a promising and practical candidate for hydrophobic modifications to various substrates.

12.
J Pathol Transl Med ; 54(1): 95-102, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31718120

RESUMEN

BACKGROUND: Pure mucinous carcinoma (PMC) is a rare type of breast cancer, estimated to represent 2% of invasive breast cancer. PMC is typically positive for estrogen receptors (ER) and progesterone receptors (PR) and negative for human epidermal growth factor receptor 2 (HER2). The clinicopathologic characteristics of HER2-positive PMC have not been investigated. METHODS: Pathology archives were searched for PMC diagnosed from January 1999 to April 2018. Clinicopathologic data and microscopic findings were reviewed and compared between HER2-positive PMC and HER2-negative PMC. We also analyzed the differences in disease-free survival (DFS) and overall survival according to clinicopathologic parameters including HER2 status in overall PMC cases. RESULTS: There were 21 HER2-positive cases (4.8%) in 438 PMCs. The average tumor size of HER2-positive PMC was 32.21 mm (± 26.55). Lymph node metastasis was present in seven cases. Compared to HER2-negative PMC, HER2-positive PMC presented with a more advanced T category (p < .001), more frequent lymph node metastasis (p = .009), and a higher nuclear and histologic grade (p < .001). Microscopically, signet ring cells were frequently observed in HER2-positive PMC (p < .001), whereas a micropapillary pattern was more frequent in HER2-negative PMC (p = .012). HER2-positive PMC was more frequently negative for ER (33.3% vs. 1.2%) and PR (28.6% vs. 7.2%) than HER2-negative PMC and showed a high Ki-67 labeling index. During follow-up, distant metastasis and recurrence developed in three HER2-positive PMC patients. Multivariate analysis revealed that only HER2-positivity and lymph node status were significantly associated with DFS. CONCLUSIONS: Our results suggest that HER2-positive PMC is a more aggressive subgroup of PMC. HER2 positivity should be considered for adequate management of PMC.

13.
Int J Dent Hyg ; 18(1): 52-61, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31394021

RESUMEN

OBJECTIVES: While common in the elderly, dry mouth can negatively affect their oral health and nutritional status. Self-administered oral care by the elderly can improve their oral health and prevent oral diseases. This study aimed to identify the content of oral health promotion programmes for community-dwelling elderly and to determine which programmes are effective in improving oral health decreasing xerostomia in these populations. METHODS: A systematic literature search and meta-analysis was conducted using the PRISMA guidelines. All available papers published in English or Korean were searched between 1 June and 13 June 2018. The relevant databases in PubMed Central, MEDLINE, CINAHL, the Cochrane Library and Embase, as well as open dissertation and academic searches, were performed. Data were extracted from the selected studies based on PICOS, and the health outcomes of the elderly were subjected to meta-analysis categorized by salivary secretion rates and oral health-related quality of life (OHQoL). RESULTS: A total of nine studies had sufficient data for a systematic review and meta-analysis. The intervention programmes consisted mainly of oral health promotion programmes, mouth exercises, toothbrushing and salivary massage. The meta-analysis indicated that elderly participating in oral health programmes had significantly increased oral salivary secretion rates and OHQoL (effect sizes of 0.63 and 0.80, respectively). CONCLUSIONS: Oral health promotion programmes in the elderly provide the positive effects of relieving dry mouth and improving OHQoL. This systematic review confirmed the contents and effects of the oral health promotion programmes provided to community-dwelling elderly.


Asunto(s)
Salud Bucal , Xerostomía , Anciano , Humanos , Vida Independiente , Calidad de Vida , Cepillado Dental
14.
Ultrason Sonochem ; 62: 104861, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31796325

RESUMEN

Emodin is a bioactive compound with strong anti-inflammatory and antioxidant properties. Micellar casein is casein concentrates close to the native state of casein micelles. The interaction of emodin and micellar casein under heat treatment in the absence and presence of ultrasound was investigated, and the properties of microencapsulated emodin in micellar casein were compared. Fluorescence experiments proved that the major interaction between emodin and micellar casein was through hydrophobic forces under heat treatment in the absence and presence of ultrasound. However, ΔH, ΔS and ΔG of emodin-casein complexation without sonication were higher than those with sonication, in contradiction to binding constants. The particle sizes of emodin-casein complexes in the presence of ultrasound were smaller than those without sonication, while the specific surface area showed an opposite trend. As to encapsulation, emodin-casein capsules under heat-sonication treatment showed higher antioxidant properties than those of heat treatment alone under similar experimental conditions. Interestingly, micellar casein-emodin encapsulation in the presence of ultrasound showed a lower release rate of emodin in gastrointestinal conditions than that without ultrasound at the emdoin concentration of 10 µmol per gram casein. Ultrasound has been shown to be a potential processing technology for customizing the release kinetics of bioactive compounds.

15.
J Nanosci Nanotechnol ; 20(3): 1685-1696, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31492331

RESUMEN

The process in which the nanofiber membrane is used to remove heavy metal ions and separation of oil-water solution is analyzed. Herein, smooth structures are induced by rGO-g-PAO sheets, which could be attributed to the strong interaction between P(AN-MA) and rGO-g-PAO. It is rewarding to note that the P(AN-MA)/rGO-g-PAO nanofiber membrane would exhibit superhydrophilic traits in the air and ultra-low oil-adhesive traits underwater when the concentration of P(AN-MA) and PAO is 13 wt.% and 0.3 wt.%, respectively. The amidoxime (-C(NH2) NOH) groups on the membrane surface can efficiently adsorb copper (Cu(II)) (1.65 mmol/g) and chromium (Cr(VI)) (4.70 mmol/g) ions in the waste water. Meanwhile, the P(AN-MA)/rGO-g-PAO nanofiber membrane exhibits ultrahigh flux (~6150 LMH), satisfying rejection rate (~97%) and outstanding flux recovery ratio (~99%) in separating oil water emulsion.

16.
Eur Radiol ; 30(1): 588-599, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31418086

RESUMEN

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the diagnostic outcomes and complication rates and to identify potential covariates that could influence these results for computed tomography (CT)-guided core needle biopsy (CNB) of mediastinal masses. METHODS: A computerized search of the PubMed and EMBASE databases was performed to identify original articles on the use of CT-guided CNB for mediastinal mass. The pooled proportions of the diagnostic yield and accuracy were assessed using random effects modeling. We assessed the pooled proportion of complication rates using random effects or fixed effects modeling. Multivariate meta-regression analyses were performed to evaluate the potential sources of heterogeneity. RESULTS: Eighteen eligible studies (1310 patients with 1345 CT-guided CNBs) were included. The pooled proportions of the diagnostic yield and accuracy of CT-guided CNB for mediastinal masses were 92% (18 studies, 1345 procedures) and 94% (15 studies, 803 procedures), respectively. In the subgroup analysis, the pooled proportions of the total complication rate and major complication rate were 13% and 2%, respectively. In the meta-regression analyses, the number of tissue samplings (odds ratio [OR], 3.3; p = 0.03), real-time fluoroscopy-guided (OR, 2.1; p = 0.02), and percentage of lymphoma (OR, 2.2; p < 0.001) for diagnostic yield, number of tissue samplings (OR = 2.0, p = 0.02) for diagnostic accuracy, and biopsy needle diameter (OR, 2.5; p = 0.002) for total complication rate were all sources of heterogeneity. CONCLUSIONS: CT-guided CNB for mediastinal mass demonstrates high diagnostic outcomes and low complication rates. The use of 20-gauge biopsy needles and obtaining ≥ 3 samples may be recommended to improve diagnostic outcomes and decrease complication rates. KEY POINTS: • The pooled estimates of diagnostic yield and accuracy of computed tomography (CT)-guided core needle biopsy (CNB) for mediastinal masses are 92% and 94%, respectively. • The pooled estimates of the total complication rate and major complication rate were 13% and 2%, respectively. • The use of a 20-gauge needle and ≥ 3 tissue samplings are recommended for CT-guided mediastinal CNB to achieve high diagnostic outcomes and lower complication rates.

17.
Sci Rep ; 9(1): 18273, 2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31797893

RESUMEN

The clinical significance of physiologic Fluorine-18-fluorodeoxyglucose (18F-FDG) intestinal uptake (IU) based on the predicted link with gut microbiota dysbiosis and inflammatory cytokine production was investigated in a cohort of breast cancer patients. A total of 114 patients were visually classified into the lower or higher IU group. The maximum and mean standardized uptake values of total bowel (TB SUVmax and TB SUVmean) were measured. The gut microbial abundance of the Citrobacter genus of the Enterobacteriaceae family showed a significant positive correlation with TB SUVmax and TB SUVmean (q = 0.021 and q = 0.010). The unclassified Ruminococcaceae showed a significant negative correlation with TB SUVmax (q = 0.010). The level of tumor necrosis factor alpha (TNF-α) was significantly increased in the high IU group (p = 0.017). The TNF-α levels showed a significant positive correlation with TB SUVmax (rho = 0.220 and p = 0.018) and TB SUVmean (rho = 0.250 and p = 0.007). Therefore, our findings suggest that the physiologic intestinal uptake may reflect subclinical inflammation and differences in the composition of the gut microbiome in breast cancer patients.

18.
Contrast Media Mol Imaging ; 2019: 1760184, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31787861

RESUMEN

Pictilisib (GDC-0941) is an inhibitor of phosphatidylinositol 3-kinase (PI3K), part of a signaling cascade involved in breast cancer development. The purpose of this study was to evaluate the pharmacokinetics of pictilisib noninvasively by radiolabeling it with 11C and to assess the usability of the resulting [11C]-pictilisib as a positron-emission tomography (PET) tracer to screen for pictilisib-sensitive tumors. In this study, pictilisib was radiolabeled with [11C]-methyl iodide to obtain 11C-methylated pictilisib ([11C]-pictilisib) using an automated synthesis module with a high radiolabeling yield. Considerably higher uptake ratios were observed in MCF-7 (PIK3CA mutation, pictilisib-sensitive) cells than those in MDA-MB-231 (PIK3CA wild-type, pictilisib-insensitive) cells at all evaluated time points, indicating good in vitro binding of [11C]-pictilisib. Dynamic micro-PET scans in mice and biodistribution results showed that [11C]-pictilisib was mainly excreted via the hepatobiliary tract into the intestines. MCF-7 xenografts could be clearly visualized on the static micro-PET scans, while MDA-MB-231 tumors could not. Biodistribution results of two xenograft models showed significantly higher uptake and tumor-to-muscle ratios in the MCF-7 xenografts than those in MDA-MB-231 xenografts, exhibiting high in vivo targeting specificity. In conclusion, [11C]-pictilisib was first successfully prepared, and it exhibited good potential to identify pictilisib-sensitive tumors noninvasively, which may have a great impact in the treatment of cancers with an overactive PI3K/Akt/mTOR signal pathway. However, the high activity in hepatobiliary system and intestines needs to be addressed.

19.
Invest New Drugs ; 2019 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-31832851

RESUMEN

Dysfunction of natural killer (NK) cells is associated with poor prognosis in hepatocellular carcinoma (HCC). We explored the phenotypic and functional characteristics of peripheral blood NK cells in HCC patients following sorafenib treatment.Peripheral blood samples were collected from 60 HCC patients in a single centre (2015~2017) and 45 healthy donors. The percentage and cytoplasmic granule production of NK cells were analysed. Subset proportions were evaluated for their associations with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), time to progression, and median overall survival (OS).Compared with baseline, the percentages of total and CD56dimCD16+ NK cells increased after two months of treatment, while the percentage of CD56brightCD16- NK cells decreased, leading to a dramatically reduced ratio of CD56bright and CD56dim NK cells (ratiobri/dim). Patients with low ratiobri/dim exhibited better mRECIST responses and longer median OS than those with high ratiobri/dim. The expression levels of granzyme B and perforin in total NK cells and in both subsets of cells were increased after treatment.This study showed that sorafenib could affect the proportions and functions of peripheral CD56brightCD16- and CD56dimCD16+ NK cells, which was associated with the outcomes including OS of HCC patients.

20.
Artículo en Inglés | MEDLINE | ID: mdl-31870653

RESUMEN

BACKGROUND AND AIMS: Since there is a shortage of liver donors, we investigated recurrence patterns and outcomes after liver resection (LR) to determine the feasibility of salvage liver transplantation (SLT). METHODS: We analyzed 468 patients with hepatocellular carcinoma (HCC) within the Milan criteria (MC) who were mainly associated with Hepatitis B virus infection (76.3%) and had undergone curative LR as an initial treatment. RESULTS: The overall survival (OS) rates were 86.6% and 67.4% at 5 and 10 years after LR, respectively. During a median follow-up of 59 months, 211 patients experienced recurrences including 175 (37.4%) within MC and 36 (7.7%) beyond MC. Survival was lowest in patients with beyond MC-recurrence followed by within MC- and no-recurrence groups (26.5%, 86.6%, and 94.7% at 5 years, respectively, P<0.001). Independent pathologic predictors of recurrence beyond MC were the presence of satellite nodules, microvascular invasion, and unfavorable gross findings (multinodular confluent and infiltrative) (all, P<0.05). Patients with all three risk factors experienced recurrence with the highest cumulative incidence of mortality. Among 173 patients with recurrence within MC, the cumulative incidence of HCC progression beyond MC despite resection and locoregional treatment (LRT) was 29% and 60% at 5 and 10 years after recurrence, respectively, and their 10-year OS rate was 25.8%. CONCLUSION: Curative LR achieved a 5-year survival of>85% in patients with transplantable HCC, but early SLT after recurrence within MC is advocated because of poor survival and high risk of progression thereafter. Further, prophylactic LT could be considered for those with high risk of recurrence.

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