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An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality.
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The triglyceride-glucose index (TyGI) is a novel indicator of insulin resistance, which has been associated with an increased risk of cardiovascular diseases. The aim of this meta-analysis was to determine the association between TyGI and the prognosis of patients with heart failure (HF). Cohort studies relevant to the aim of the meta-analysis were retrieved by searching electronic databases, including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data, incorporating the influence of between-study heterogeneity. Twelve studies involving 20,639 patients with HF were included. Pooled results showed that compared to patients with the lowest category of TyGI at baseline, those with the highest TyGI index were associated with a higher risk of all-cause mortality during follow-up (relative risk [RR] 1.71, 95% confidence interval [CI] 1.46 - 2.00; P < 0.001; I² = 55%). Sensitivity analyses limited to studies after adjustment for confounding factors showed similar results (RR 1.89, 95% CI 1.67 - 2.21; P < 0.001; I² = 13%). Subsequent meta-analyses also showed that a high TyGI at baseline was related to the incidence of cardiovascular death (RR 1.87, 95% CI 1.42 - 2.47; P < 0.001; I² = 57%), HF rehospitalization (RR 1.33, 95% CI 1.04 - 1.69; P < 0.02; I² = 46%), and major adverse cardiovascular events (RR 1.69, 95% CI 1.39 - 2.06; P < 0.001; I² = 17%) during follow-up. In conclusion, a high TyGI may be associated with a poor clinical prognosis for patients with HF.
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Objective: It was to explore the ultrasonic characteristics of complications of twin pregnancies with monochorionic diamniotic (MCDA) during various pregnancy periods and the differences in pregnancy outcomes. Methods: One hundred pregnant women with MCDA were included in the study. They were rolled into a complication group (44 cases) and a non-complication group (56 cases) according to whether they had complications. The pulsatility index (PI), resistance index (RI), and systolic/diastolic (S/D) values of ultrasound in pregnant women and the final neonatal situation at each time period were compared and analyzed. Results: In pregnant women with twin-twin transfusion syndrome (TTTS), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05). Compared to the group without complications, the incidence of neonatal death was significantly increased in the complication group, and the newborn's weight, length, head circumference, and Apgar score were significantly lower (P < .05). In pregnant women with selective intrauterine growth restriction (sIUGR), the RI and PI values of the larger twin were significantly higher than those of the smaller twin during pregnancy, and S/D values were significantly lower (P < .05). The newborns in the group without complications had significantly higher body weight, length, and head circumference (P < .05). In pregnant women with gestational diabetes mellitus (GDM), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), and there were no significant differences in other indicators compared to the group without complications. In pregnant women with premature rupture of membrane (PROM), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), but the newborns in the group without complications had significantly higher weight, length, Apgar score, and lower incidence of neonatal death (P < .05). In pregnant women with preeclampsia (PE), there was no significant difference in RI and S/D values between the larger and smaller twin during pregnancy (P > .05), and there were no significant differences in other indicators compared to the group without complications (P > .05). Conclusion: Pregnant women with sIUGR had significantly higher RI and PI values in the larger twin and significantly lower S/D values compared to the smaller twin during pregnancy, while no significant differences were observed for other complications. The combination of TTTS and PROM decreased the birth weight, body length, head circumference, and Apgar score of twins and increased the mortality rate.
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Transfusión Feto-Fetal , Resultado del Embarazo , Embarazo Gemelar , Humanos , Femenino , Embarazo , Resultado del Embarazo/epidemiología , Adulto , Transfusión Feto-Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico por imagen , Ultrasonografía Prenatal , Complicaciones del Embarazo , Recién NacidoRESUMEN
This work is an update and extension of the previously published article "Ultralong Oxford Nanopore Reads Enable the Development of a Reference-Grade Perennial Ryegrass Genome Assembly" by Frei et al. The published genome assembly of the doubled haploid perennial ryegrass (Lolium perenne L.) genotype Kyuss (Kyuss v1.0) marked a milestone for forage grass research and breeding. However, order and orientation errors may exist in the pseudo-chromosomes of Kyuss, since barley (Hordeum vulgare L.), which diverged 30 million years ago from perennial ryegrass, was used as the reference to scaffold Kyuss. To correct for structural errors possibly present in the published Kyuss assembly, we de novo assembled the genome again and generated 50-fold coverage high-throughput chromosome conformation capture (Hi-C) data to assist pseudo-chromosome construction. The resulting new chromosome-level assembly Kyuss v2.0 showed improved quality with high contiguity (contig N50 = 120 Mb), high completeness (total BUSCO score = 99%), high base-level accuracy (QV = 50), and correct pseudo-chromosome structure (validated by Hi-C contact map). This new assembly will serve as a better reference genome for Lolium spp. and greatly benefit the forage and turf grass research community.
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Bacterial wilt, caused by Xanthomonas translucens pv. graminis (Xtg), is a serious disease of economically important forage grasses, including Italian ryegrass (Lolium multiflorum Lam.). A major QTL for resistance to Xtg was previously identified, but the precise location as well as the genetic factors underlying the resistance are yet to be determined. To this end, we applied a bulked segregant analysis (BSA) approach, using whole-genome deep sequencing of pools of the most resistant and most susceptible individuals of a large (n = 7484) biparental F2 population segregating for resistance to Xtg. Using chromosome-level genome assemblies as references, we were able to define a ~300 kb region highly associated with resistance on pseudo-chromosome 4. Further investigation of this region revealed multiple genes with a known role in disease resistance, including genes encoding for Pik2-like disease resistance proteins, cysteine-rich kinases, and RGA4- and RGA5-like disease resistance proteins. Investigation of allele frequencies in the pools and comparative genome analysis in the grandparents of the F2 population revealed that some of these genes contain variants with allele frequencies that correspond to the expected heterozygosity in the resistant grandparent. This study emphasizes the efficacy of combining BSA studies in very large populations with whole genome deep sequencing and high-quality genome assemblies to pinpoint regions associated with a binary trait of interest and accurately define a small set of candidate genes. Furthermore, markers identified in this region hold significant potential for marker-assisted breeding strategies to breed resistance to Xtg in Italian ryegrass cultivars more efficiently.
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Resistencia a la Enfermedad , Lolium , Enfermedades de las Plantas , Xanthomonas , Lolium/genética , Lolium/microbiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Xanthomonas/fisiología , Sitios de Carácter Cuantitativo/genética , Genes de Plantas/genética , Mapeo CromosómicoRESUMEN
Subarachnoid hemorrhage (SAH) is a hemorrhagic cerebrovascular disease with an extremely poor prognosis. The molecular mechanism and biomarkers involved in neurological outcome after SAH still need to be explored. This study assessed the microRNA expression characteristics of SAH patients with different neurological outcomes by meta-analysis. Public databases were searched from database inception until December 2022. The study reported that microRNA expression data in SAH patients with different neurological outcomes were included in the analysis. The differential expression of miRNAs was evaluated by meta-analysis. Overrepresentation analysis was performed for the targeted genes of significant miRNAs. The XGBoost algorithm was used to assess the predictive ability for neurological outcomes with clinical characteristics and significantly expressed miRNAs. Seven studies were finally included in the meta-analysis. The results showed that the levels of miR-152-3p (SMD: - 0.230; 95% CI - 0.389, - 0.070; padj = 0.041), miR-221-3p (SMD: - 0.286; 95% CI - 0.446, - 0.127; padj = 0.007), and miR-34a-5p (SMD: - 0.227; 95% CI - 0.386, - 0.067; padj = 0.041) were significantly lower in SAH patients with good neurological outcomes than in those with poor neurological outcomes. The PI3K-AKT signaling pathway may have an important role in neurological recovery after SAH. Based on the XGBoost algorithm, the neurological outcome could be accurately predicted with clinical characteristics plus the three miRNAs. The expression levels of miR-152-3p, miR-221-3p, and miR-34a-5p were significantly lower in patients with good neurological outcomes than in those with poor outcomes. These miRNAs can serve as potential predictive biomarkers for neurological outcomes. The molecular mechanism and biomarkers involved in neurological outcome after SAH still need to be explored. Our study analyzed microRNA expression characteristics of SAH patients with different neurological outcomes by meta-analysis. After analyze studies reporting the microRNA expression data in SAH patients with different neurological outcomes, results show that the levels of miR-152-3p, miR-221-3p, and miR-34a-5p were significantly lower in SAH patients with good neurological outcomes than in those with poor neurological outcomes. The PI3K-AKT signaling pathway may have an important role in neurological recovery after SAH. Based on the XGBoost algorithm, the neurological outcome could be accurately predicted with clinical characteristics plus the three miRNAs.
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MicroARNs , Hemorragia Subaracnoidea , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , BiomarcadoresRESUMEN
Z-ligustilide (or ligustilide) is found in Angelica sinensis (Oliv.) Diels and may exert potential benefits in cancer treatment. Previous research has reported that ligustilide has anti-cancer effects on several types of cancer cells. However, studies of ligustilide on oral cancer cells have not been reported, especially under hypoxic conditions. This study focuses on the molecular mechanism of ligustilide-induced apoptosis in hypoxic oral cancer cells. We found that in hypoxic TW2.6 cells, ligustilide inhibited cell migration and induced caspase-dependent apoptosis. Accumulation of c-Myc accompanied by BH3-only members suggests that ligustilide may induce c-Myc-dependent apoptosis. In addition, we reported that ligustilide has an effect on ER-stress signaling. By using inhibitors of c-Myc, IRE1α, and ER-stress inhibitors, we found that cell morphologies or cell viability were rescued to some degree. Moreover, ligustilide is able to increase the expression of γ-H2AX and enhance the occurrence of DNA damage in oral cancer cells after radiation treatment. This result suggests that ligustilide has potential as a radiation sensitizer. Altogether, we propose that ligustilide may induce c-Myc-dependent apoptosis via ER-stress signaling in hypoxic oral cancer cells.
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BACKGROUND: Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases. METHODS: This population-based, nationwide cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases. RESULTS: A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was a significantly decreased risk of thyroid diseases among ADT users compared with non-ADT users (adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p < 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p < 0.001). CONCLUSIONS: The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.
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Neoplasias de la Próstata , Enfermedades de la Tiroides , Antagonistas de Andrógenos/efectos adversos , Andrógenos , Estudios de Cohortes , Humanos , Masculino , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/complicaciones , Enfermedades de la Tiroides/epidemiologíaRESUMEN
BACKGROUND: Accurate and effective biomarkers for the prognosis of patients with hepatocellular carcinoma (HCC) are poorly identified. A network-based gene signature may serve as a valuable biomarker to improve the accuracy of risk discrimination in patients. METHODS: The expression levels of cancer hallmarks were determined by Cox regression analysis. Various bioinformatic methods, such as GSEA, WGCNA, and LASSO, and statistical approaches were applied to generate an MTORC1 signaling-related gene signature (MSRS). Moreover, a decision tree and nomogram were constructed to aid in the quantification of risk levels for each HCC patient. RESULTS: Active MTORC1 signaling was found to be the most vital predictor of overall survival in HCC patients in the training cohort. MSRS was established and proved to hold the capacity to stratify HCC patients with poor outcomes in two validated datasets. Analysis of the patient MSRS levels and patient survival data suggested that the MSRS can be a valuable risk factor in two validated datasets and the integrated cohort. Finally, we constructed a decision tree which allowed to distinguish subclasses of patients at high risk and a nomogram which could accurately predict the survival of individuals. CONCLUSIONS: The present study may contribute to the improvement of current prognostic systems for patients with HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Anciano , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/mortalidad , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Transducción de Señal/genéticaRESUMEN
(1) Background: In Taiwan, prostate cancer is a major malignancy with an increasing incidence among men. This study explores the medical utilization of emergency departments among patients with prostate cancer in Taiwan. (2) Methods: This nationwide, population-based study was conducted via a cross-sectional method based on the Registry for Catastrophic Illness Patient Database from Taiwan's National Health Insurance Research Database. Patients with newly diagnosed prostate cancer between 1997 and 2013 were enrolled in the study and divided into four treatment-related groups. The rate of emergency department presentation, disease categorization of emergency department visits, emergency department-related medical expenditures, and temporal trends were investigated. (3) Results: A total of 18,728 patients with prostate cancer were identified between 1997 and 2013, for whom 13,098 emergency department visits were recorded. The number of emergency department visits increased during the study period. The incidence rate for the medical utilization of emergency department visits was 822 per 1000 people during the study period. The incidence rates for patients with prostate cancer in the radical prostatectomy, radiotherapy, androgen deprivation therapy, and chemotherapy groups were 549, 1611, 1101, and 372, respectively. The average medical expenditure per emergency department visit was TWD 3779.8 ± 5116.2, and the expenditure was recorded for the chemotherapy group at TWD 4690.8 ± 7043.3. The most common disease diagnoses among patients with prostate cancer who presented to the emergency department were injury/poisoning (16.79%), genitourinary disorders (10.66%), and digestive disorders (10.48%). (4) Conclusions: This nationwide population-based study examined the emergency department visits of patients with prostate cancer in Taiwan, providing useful information for improving the quality of medical care.
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Antagonistas de Andrógenos , Neoplasias de la Próstata , Estudios Transversales , Servicio de Urgencia en Hospital , Humanos , Masculino , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/terapia , Taiwán/epidemiologíaRESUMEN
BACKGROUND: Reduced heart rate (HR) increase (HRI), recovery (HRR), and higher resting HR are associated with cardiovascular (CV) disease, but causal inferences have not been deduced. We investigated causal effects of HRI, HRR, and resting HR on CV risk, all-cause mortality (ACM), atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke (IS) using Mendelian Randomization. METHODS: 11 variants for HRI, 11 for HRR, and two sets of 46 and 414 variants for resting HR were obtained from four genome-wide association studies (GWASs) on UK Biobank. We performed a lookup on GWASs for CV risk and ACM in UK Biobank (N = 375,367, 5.4% cases and N = 393,165, 4.4% cases, respectively). For CAD, AF, and IS, we used publicly available summary statistics. We used a random-effects inverse-variance weighted (IVW) method and sensitivity analyses to estimate causality. RESULTS: IVW showed a nominally significant effect of HRI on CV events (odds ratio [OR] = 1.0012, P = 4.11 × 10-2) and on CAD and AF. Regarding HRR, IVW was not significant for any outcome. The IVW method indicated statistically significant associations of resting HR with AF (OR = 0.9825, P = 9.8 × 10-6), supported by all sensitivity analyses, and a nominally significant association with IS (OR = 0.9926, P = 9.82 × 10-3). CONCLUSION: Our findings suggest no strong evidence of an association between HRI and HRR and any outcome and confirm prior work reporting a highly significant effect of resting HR on AF. Future research is required to explore HRI and HRR associations further using more powerful predictors, when available.
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Janus 2D transition metal dichalcogenide (TMD) is a new generation 2D material with a unique asymmetric structure. This asymmetric structure (or out-off plane symmetric geometry) of Janus 2D TMD has been reported to yield tunable electronic properties through strain and electric field, which can also be applied in gas sensing. In this work, we performed DFT calculations to investigate the gas sensing property of cyclohexane and acetone on MoS2 and Janus MoSSe monolayers under external electric fields. Our results show that cyclohexane possesses slightly larger adsorption energy on pristine MoS2 and Janus MoSSe monolayers than acetone without external electric fields. After applying the external electric fields, the adsorption energy for cyclohexane on MoS2 shows no enhancement. However, the adsorption energy of acetone shows the most substantial enhancement on the Janus MoSSe monolayer. We found that the dipole moment orientations of adsorbates and the monolayer can strongly interact with the external electric fields. Hence, the combination of polar adsorbate and polar material, i.e., acetone and Janus MoSSe, demonstrates the most vital sensitivity under the applied bias. On the other hand, the non-polar adsorbate and non-polar material combination show a negligible effect on external bias. These findings can be applied to the design of gas sensors in the future through polar materials.
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This study aimed to investigate the efficacy and safety of drug-eluting beads (DEB) transarterial chemoembolization (TACE) treatment in Chinese intrahepatic cholangiocarcinoma (ICC) patients.37 ICC patients underwent DEB-TACE treatment in CTILC study (registered on clinicaltrials.gov with registry No. NCT03317483) were included in this present study. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was calculated from the time of DEB-TACE operation until the date of death from any causes. Liver function change and adverse events (AEs) were recorded during and after DEB-TACE operation.3 (8.1%) patients achieved complete response (CR) and 22 (59.5%) patients achieved partial response (PR), with objective response rate (ORR) of 67.6%. After DEB-TACE treatment, mean OS was 376 days (95%CI: 341-412 days). Multivariate logistic regression analysis revealed that Bilobar disease (Pâ=â.040, OR: 0.105, 95% CI: 0.012-0.898) and portal vein invasion (Pâ=â.038, OR: 0.104, 95% CI: 0.012-0.881) could independently predict less possibility of ORR. Patients with ALB abnormal, TP abnormal, ALT abnormal and AST abnormal were increased at 1-week post DEB-TACE treatment (Pâ=â.034, Pâ=â.001, Pâ<â.001, Pâ=â.006, respectively), while returned to the levels at baseline after 1 to 3 months (all Pâ>â.050). Besides, most of the AEs were mild including pain, fever, vomiting, and nausea in this study.DEB-TACE was effective and well tolerated in treating ICC patients, and bilobar disease as well as portal vein invasion were independently correlated with less probability of ORR achievement.
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Neoplasias de los Conductos Biliares/terapia , Quimioembolización Terapéutica/métodos , Colangiocarcinoma/terapia , Anciano , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Doxorrubicina , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Neoplasias Hepáticas/secundario , Modelos Logísticos , Masculino , Microesferas , Persona de Mediana Edad , Invasividad Neoplásica , Vena Porta/patologíaRESUMEN
This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375-393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size ≥5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1-3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Anciano , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
The purpose of this study was to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Chinese hepatocellular carcinoma (HCC) patients and the prognostic factors for treatment response as well as survival. A total of 275 HCC patients were included in this prospective study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and progression-free survival (PFS) as well as overall survival (OS) were determined. Liver function and adverse events (AEs) were assessed before and after DEB-TACE operation. Complete response (CR), partial response (PR), and objective response rate (ORR) were 22.9%, 60.7%, and 83.6%, respectively. The mean PFS was 362 (95% CI: 34.9-375) days, the 6-month PFS rate was 89.4 ± 2.1%, while the mean OS was 380 (95% CI: 370-389) days, and the 6-month OS rate was 94.4 ± 1.7%. Multivariate logistic regression revealed that portal vein invasion (p = 0.011) was an independent predictor of worse clinical response. Portal vein invasion (p = 0.040), previous cTACE treatment (p = 0.030), as well as abnormal serum creatinine level (BCr) (p = 0.017) were independent factors that predicted worse ORR. In terms of survival, higher Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.029) predicted for worse PFS, and abnormal albumin (ALB) (p = 0.011) and total serum bilirubin (TBIL) (p = 0.009) predicted for worse OS. The number of patients with abnormal albumin, total protein (TP), TBIL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were augmented at 1 week posttreatment and were similar at 1-3 months compared with baseline. The most common AEs were pain, fever, nausea, and vomiting, and no severe AEs were observed in this study. DEB-TACE was effective and tolerable in treating Chinese HCC patients, and portal vein invasion, previous cTACE treatment, abnormal BCr, ALB, and TBIL appear to be important factors that predict worse clinical outcome.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Doxorrubicina/administración & dosificación , Neoplasias Hepáticas/terapia , Anciano , Bilirrubina/sangre , Carcinoma Hepatocelular/mortalidad , Quimioembolización Terapéutica/efectos adversos , China , Creatinina/sangre , Sistemas de Liberación de Medicamentos , Epirrubicina/administración & dosificación , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Microesferas , Persona de Mediana Edad , Vena Porta/patología , Supervivencia sin Progresión , Estudios Prospectivos , Albúmina Sérica Humana/análisis , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
YES-associated protein 1 (YAP1) plays a key role as a transcriptional coactivator in the Hippo tumor suppressor pathway. YAP1 is overexpressed in a variety of cancers and is considered to be encoded by a proto-oncogene. However, the role of YAP1 remains debatable, because both gain and loss of YAP1 expression have both been reported in breast cancer (BC). Here, we found that elevated expression of YAP1 mRNA in BC was negatively correlated with relapse-free, distant metastases-free and overall survival rates. We then knocked down or overexpressed YAP1 in human BC cells, and examined cell proliferation, apoptosis, and tumorigenic ability in vivo. We identified that YAP1 promotes cell growth and inhibits cell apoptosis of BC through the phosphatase and tensin homolog deleted on chromosome 10-AKT signaling pathway, and thus suggest that YAP1 might serve as a new target for inhibiting BC progression.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fosfohidrolasa PTEN/antagonistas & inhibidores , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Apoptosis , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Proliferación Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Mamarias Experimentales/diagnóstico , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfohidrolasa PTEN/metabolismo , Pronóstico , Proto-Oncogenes Mas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción/metabolismo , Células Tumorales Cultivadas , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: This study aimed to assess the treatment response, short-term overall survival (OS) and safety profiles of drug-eluting beads transarterial chemoembolization (DEB-TACE) in patients with secondary liver cancer. METHODS: Fifty-five patients with secondary liver cancer underwent DEB-TACE were enrolled in this prospective cohort study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST). OS was calculated from the time of DEB-TACE operation until the date of death. RESULTS: The complete response (CR) and objective response rate (ORR) at 1-3 months post DEB-TACE were 12.7% and 67.3%. Mean OS was 383 d (95% CI: 360-406), and 6-month OS rate was 93.4%±3.7%. Subgroup analysis revealed previous conventional TACE (cTACE) treatment was correlated with worse ORR (P=0.028), and it was a risk factor for ORR achievement (P=0.021). As for liver function, the percentages of abnormal TP (P=0.031), TBIL (P=0.022), ALT (P=0.002) and AST (P=0.035) were increased at 1 week post DEB-TACE compared to baseline, while these four indexes returned to baseline (all P>0.05) at 1-3 months post DEB-TACE. As to safety profiles, 41 (66.1%), 28 (45.2%), 17 (27.4%), 8 (12.9%) and 6 (9.7%) cases had pain, vomiting, fever, nausea and other adverse events (AEs) respectively during DEB-TACE operation, while 26 (41.9%), 9 (14.5%), 8 (12.9%), 4 (6.5%), 1 (1.6%) and 2 (3.2%) cases had pain, fever, vomiting, nausea, bone marrow toxicity and other AEs respectively at 1 month after DEB-TACE operation. CONCLUSIONS: DEB-TACE was efficient and well tolerated in treating patients with secondary liver cancer.
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BACKGROUND: The purpose of this study is to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with computed tomography-guided radiofrequency ablation (CT-RFA) in the treatment of hepatocellular carcinoma (HCC) using magnetic resonance diffusion weighted imaging (MR-DWI) and CT perfusion imaging (CT-PI). METHODS: From January 2008 to January 2014, a total of 522 HCC patients receiving TACE combined with CT-RFA were included in this study. All patients underwent TACE followed by CT-RFA, and 1 day before treatment and 1 month after treatment they received MR-DWI and CT-PI. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the concentration of alpha-fetoprotein (AFP). Tumor response was evaluated using the revised RECIST criteria. One-year follow-up was conducted on all patients. Receiver-operating characteristic (ROC) curve was drawn to evaluate the efficacy of TACE combined with CT-RFA for HCC using MR-DWI and CT-PI. RESULTS: Total effective rate (complete remission [CR]â+âpartial remission [PR]) of TACE combined with CT-RFA for HCC was 82.95%. HCC patients of CRâ+âPR had lower hepatic blood flow (HBF), hepatic blood volume (HBV), permeability surface (PS), hepatic arterial perfusion (HAP), and hepatic perfusion index (HPI) levels than those of SDâ+âPD, but HCC patients of CRâ+âPR had higher mean transit time (MTT) level than those of SDâ+âPD. The patients of PRâ+âCR had higher apparent diffusion coefficient (ADC) values than those of SDâ+âPD. The patients of PRâ+âCR showed lower AFP concentration than those of SDâ+âPD. ROC curve analysis indicated that the area under the curve (AUC) of AFP, HBV, PS, HAP, HPI, and ADC was more than 0.7, but the AUC of HBF, MTT, and PVP were less than 0.7. After treatment, the AFP, HBF, HBV, PS, HAP, and HPI in the HCC patients with recurrence were higher than those in the HCC patients without, but MTT and ADC in the HCC patients with recurrence were lower than those in the HCC patients without. CONCLUSION: These findings indicate that MR-DWI and CT-PI can effectively evaluate the efficacy of TACE combined with CT-RFA and postoperative recurrence of HCC.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Terapia Combinada , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Imagen de Perfusión , Estudios Prospectivos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the characteristics of enhancement of focal nodular hyperplasia (FNH) of the liver by analyzing the dynamic contrast-enhanced multislice computed tomography (MSCT) features and correlating them with pathological findings. PATIENTS AND METHODS: Nine males and 16 females with pathologically confirmed FNH and complete preoperative contrast-enhanced MSCT data were recruited for this study. The imaging features of FNH on the pre- and postcontrast MSCT were analyzed by two experienced radiologists by consensus. RESULTS: Pathology showed central scars and abnormal blood vessels in 17 and 21 of 25 lesions, respectively, while MSCT with multiphase enhancement showed central scars in eight of the 17 lesions (47.1%) and abnormal arteries or draining veins in 13 of the 21 lesions (61.9%). Furthermore, abnormal draining veins in five lesions were found to be diagnostic, which is another important finding. CONCLUSION: Multiphase scanning can provide the panorama of FNH lesions and reveal their enhancement patterns and pathological characteristics. Abnormal blood vessels within or around the lesion are demonstrated more often than central scar, and both should be observed for FNH diagnosis.
RESUMEN
The absorption in metallic gratings with subwavelength slits is theoretically investigated. Anomalous optical absorption occurs over a wide range of incident angles for both polarizations. In particular, a nearly perfect absorbance up to 99.5% with a significant bandwidth is attained for TM polarization with compound slits. Enhanced absorption is associated with extreme concentration of fields inside the structure. The respective field pattern depicts a special feature of surface plasmons excited on single interface only, which are identified as semibonding modes. The anomalous absorption is also achieved for TE polarization, when the compound grating is reduced to a simple grating. For this polarization, the nomalous absorption is attributed to the occurrence of trapped modes, with a slightly smaller absorbance (98.4%).