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1.
Disaster Med Public Health Prep ; : 1-15, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33762058

RESUMO

BACKGROUND: The aim of this study is to evaluate the clinical characteristics and outcomes in 2019 novel coronavirus patients and to help clinicians perform correct treatment and evaluate prognosis and guide the treatment. METHODS: 239 patients who were diagnosed with COVID-19 were included in this study. Patients were divided into the improvement group and the death group according to their outcome (improvement or death).Clinical characteristics and laboratory parameters were collected from medical records. Continuous variables were tested by independent sample T test, and categorical variables were analyzed by chi-square test or Fisher exact test. Cox proportional hazard regression model was used for survival analysis in death patients. The time-dependent AUC curves based on white blood cell count, lymphocyte count, white blood cell, lymphocyte count, neutrophil counts age, blood urea nitrogen and C-reactive protein were plotted. RESULTS: Efficacy evaluation indicated that 99 patients (41.4%) had deteriorated, and 140 patients (58.6%) had improved. Oxygen saturation, hemoglobin levels, infection-related indicators, lymphocyte and platelets counts, C-reactive protein, serum albumin, liver and kidney function and lactate dehydrogenase in improvement group were statistically significant between the improvement and death groups. Survival analysis revealed that comorbidities, lymphocyte counts, platelet count, serum albumin, C-reactive protein level and renal dysfunction may be risk factors in patients with COVID-19. CONCLUSION: Patients with comorbidities, lower lymphocyte counts in hemogram, platelet count and serum albumin, high C-reactive protein level and renal dysfunctionmay have higher risk to death. More attention should be givento risk management in the progression of COVID-19.

2.
Immunotherapy ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781095

RESUMO

Aim: This study explored new immunoadjuvants with stronger immune activity to enhance therapeutic effects against leukemia. Materials & methods: Whole blood and bone marrow of acute myeloid leukemia (AML) patients and healthy volunteers were collected. Isolated mononuclear cells were treated with two newly designed CpG oligodeoxynucleotides, CpG sequence 13 and 19, and known CpG oligodeoxynucleotides and analyzed via flow cytometry. Results: CpG Seq 13 and 19 possess strong immune activation and enhance the proliferation, degranulation and cytotoxicity of T cells. They also inhibit AML cell proliferation. When CpG Seq 13/19 are combined with anti-OX40 antibodies, the cytotoxicity of T cells on AML cells are further enhanced. Conclusion: CpG Seq 13 and 19 are strong immune adjuvant candidates for AML treatment.

3.
J Hazard Mater ; 414: 125549, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33676260

RESUMO

The pollution caused by the abuse of antibiotics has posed a serious threat to the ecological environment and human health, so development of effective strategies for degradation and disposal of antibiotic residues is urgently needed. In this work, penicillinase, a kind of ß-lactamase, was immobilized into zeolitic imidazolate framework-8 (ZIF-8) by self-assembly method and the catalytic performance of the ß-lactamase@ZIF-8 porous materials for degradation of penicillins has been investigated by high performance liquid chromatography coupled with mass spectrometry. The results illustrated that the catalytic activity of the encapsulated enzyme was significantly enhanced comparing with that of free enzyme. Meanwhile, the ß-lactamase@ZIF-8 exhibited excellent stability under denaturing conditions including high temperature, organic solvent and the enzyme inhibitor. The catalytic degradation mechanism of the ß-lactamase@ZIF-8 for penicillins has been probed and verified, and it has been found that the Zn (II) ion on ZIF-8 frameworks could form the complex with the target molecule, which weakened the bond of the four-membered ß-lactam ring in the penicillin molecule, and thus enhanced the degradation efficiency of the enzyme. This work provided a promising strategy for eliminating the penicillin residues in water environment.

4.
Mol Immunol ; 132: 199-208, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33454107

RESUMO

AIM: The balance between Th17 cells and T regulatory (Treg) cells has emerged as a prominent factor in regulating cancer development. However, the effect of CpG oligodeoxynucleotides (ODNs) on the differentiation of Treg/Th17 cells has not been well studied. We sought here to explore the function of CpG ODNs in the differentiation of Tregs and Th17 cells in vitro and in vivo. METHODS: Mouse spleen cells were cultured with anti-CD3 monoclonal antibodies in vitro. Tregs and Th17 cell differentiation was induced by transforming growth factor (TGF)-ß and interleukin (IL)-2, or TGF-ß, IL-6, and IL-23, respectively. Then cells were treated with two CpG ODNs, CpG 1982, or CpG 1826. FBL-3-inoculated C57Bl/6 mice were treated with CpG 1826, tumor vaccine, or combination of CpG 1826 and tumor vaccine. After treatment, spleen cells and serum were isolated, and Tregs/Th17 cells were detected by flow cytometry. The expression of forkhead box P3 (Foxp3), retinoid-related orphan receptor gamma-t (RORγt), IL-10, and IL-17 mRNA was measured by real-time PCR, and protein levels were measured by Western blot and enzyme-linked immunosorbent assay. RESULTS: The frequency of Treg cells increased significantly (p < 0.05) in the FBL-3-inoculated leukemia mouse model compared with control mice, whereas the frequency of Th17 cells did not change. Median survival of mice after treatment with CpG 1826 and tumor vaccine was significantly prolonged compared with that of control mice (p < 0.05). The frequency of induced Treg cells decreased after treatment with CpG 1826, whereas the frequency of Th17 cells induced by cytokines in vitro and in the murine leukemia model increased following treatment with CpG 1826. Furthermore, after treatment with CpG 1826, the mRNA and protein levels of Foxp3 and IL-10 decreased significantly both in vitro and in vivo (p < 0.05), whereas those of RORγt and IL-17 increased significantly (p < 0.05). CONCLUSION: CpG 1826 may inhibit the differentiation of Treg cells induced by cytokines, promote the differentiation of Th17 cells in vitro and in murine leukemia models, and prolong the median survival of mice with leukemia.

5.
Theranostics ; 11(3): 1396-1411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391541

RESUMO

Rationale: circular RNAs (circRNAs) have been demonstrated to play a crucial role in cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. The aim of present study is to investigate the role of circular RNAs in KIAA1429-mediated HCC progression. Methods: RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined in vitro and in vivo. RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq. Results: Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells in vitro and in vivo, while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, and thus inhibited the expression of MMP1, ultimately contributing to inhibition of HCC progression. Conclusion: Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.

6.
Brain Behav ; 11(3): e02032, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33438838

RESUMO

INTRODUCTION: Thallium poisoning is a rare occurrence. Therefore, thallium poisoning is easily misdiagnosed and is often accompanied by a series of serious sequelae and can even result in death in severe cases. Here, we report long-term follow-up of a case of a patient who was poisoned with thallium on two separate occasions. METHODS: A 43-year-old man was initially misdiagnosed as gastroenteritis, diabetic peripheral neuropathy, and Guillain-Barré Syndrome (GBS) within 21 months. The correct diagnosis was confirmed by blood and urine thallium assays. After Prussian blue treatment, thallium was undetectable in the blood by day 60. Following this investigation, a criminal suspect confessed to two instances of adulterating thallium sulfate in the patient's beverage. A 6-year follow-up was performed after discharge, and a comprehensive literature was review. RESULTS: We found that the original gastrointestinal symptoms, skin lesions, and hair loss were reversed and had recovered, except for residual neurologic damage, even with long-term rehabilitation. DISCUSSION: Thallium intoxication may have been initially identified if neurologic symptoms had occurred concurrently with gastrointestinal and cutaneous symptoms. Neurologic damage represented the main sequelae of thallium poisoning in our present case report.

7.
Anal Chem ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347748

RESUMO

Plasmonic materials with highly confined electromagnetic fields at resonance wavelengths have been widely used to enhance Raman scattering signals. To achieve the maximum enhancement, the resonance peaks of the plasmonic materials should overlap with the excitation and emission wavelengths of target molecules, which is difficult for most of the plasmonic materials possessing a few narrow resonance peaks. Here, we report an ultrabroadband plasmonic metamaterial absorber (BPMA) that can absorb 99% of the incident light energy and excite plasmon resonance from the ultraviolet to near-infrared range (250-1900 nm), which allows us to observe efficient plasmon-enhanced Raman scattering (PERS) with any excitation sources. As demonstrated by the investigation on a self-assembled monolayer of the nonresonant molecule 4-mercaptobenzonitrile, the BPMA exhibits high PERS performance with a detection limit of down to 10-12 M under any excitation sources of three different lasers and excellent uniformity (∼5.51%) and reproducibility (∼5.50%), which corroborates the potential for high-throughput production with low cost and at a large scale. This work offers a novel platform for anti-interference PERS analysis in dynamic and complex environments.

8.
Gynecol Minim Invasive Ther ; 9(3): 118-122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101911

RESUMO

Objective: The objective of the study was to evaluate the effects of recurrent hydrosalpinx after proximal tubal ligation and distal salpingostomy on the outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Materials and Methods: Seven hundred and twenty-six patients with hydrosalpinx undergoing laparoscopic surgery before IVF were enrolled in the study. Five hundred and sixty-two patients treated with proximal tubal ligation and distal salpingostomy were included in Group A. One hundred and sixty-four cases managed with salpingectomy were grouped into Group B. Group A were further divided into two subgroups. One hundred and forty-six patients in Group A1 had a recurrence of hydrosalpinx. Four hundred and sixteen patients in Group A2 had no repetition of hydrosalpinx. We compared the pregnancy outcomes of their subsequent fresh embryo transfer cycles among the three groups. Results: There were no significant differences among the three groups in terms of age, body mass index (23.56 ± 3.27 vs. 23.13 ± 3.42 vs. 23.63 ± 3.73, P = 0.195), basal hormone level (7.03 ± 1.75 vs. 7.08 ± 2.26 vs. 7.44 ± 2.93, P = 0.195), antral follicle count (12.25 ± 5.92 vs. 12.63 ± 5.71 vs. 11.70 ± 4.98, P = 0.188), duration of gonadotropin (Gn) (11.19 ± 2.1 vs. 10.93 ± 1.84 vs. 10.79 ± 2.03, P = 0.182), consumption of Gn (2136.73 ± 855.65 vs. 1997.15 ± 724.72 vs. 2069.05±765.12 , P = 0.14), endometrial thickness (1.1 ± 0.27 vs. 1.1 ± 0.24 vs. 1.1 ± 0.17, P = 0.352), base follicle-stimulating hormone (6.21 ± 3.43 vs. 6.52 ± 3.20 vs. 5.89 ± 3.10, P = 0.1), number of embryos transferred (1.87 ± 0.36 vs. 1.83 ± 0.42 vs. 1.88 ± 0.37, P = 0.224), and number of high-grade embryos (3.77 ± 2.42 vs. 4.01 ± 2.72 vs. 4.17 ± 2.74, P = 0.41). No differences were detected in clinical pregnancy rate (50% vs. 54.8% vs. 50%, P = 0.439), the live birth rate (86.3% vs. 82.0% vs. 87.8%, P = 0.398), fertilization rate (64.1% vs. 64.4% vs. 64.7%, P = 0.928), and biochemical pregnancy rate (4% vs. 4.5% vs. 7%, P = 0.332) among the three groups. Conclusion: The recurrence of hydrosalpinx after tubal ligation does not affect the outcomes of IVF/ICSI. It is not necessary to worry about the effect of recurrent hydrosalpinx on pregnancy outcomes of IVF/ICSI that may due to the spread of inflammation through lymphatic circulation or blood circulation.

9.
Macromol Rapid Commun ; : e2000428, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029823

RESUMO

Lignin is an aromatic-rich biomass polymer that is cheap, abundant, and sustainable. However, its application in the solid electrolyte field is rare due to challenges in well-defined polymer synthesis. Herein, the synthesis of lignin-graft-poly(ethylene glycol) (PEG) and its conductivity test for a solid electrolyte application are demonstrated. The main steps of synthesis include functionalization of natural lignin's hydroxyl to alkene, followed by graft-copolymerization of PEG thiol to the lignin via photoredox thiol-ene reaction. Two lignin-graft-PEGs are prepared having 22 wt% lignin (lignin-graft-PEG 550) and 34 wt% lignin (lignin-graft-PEG 2000). Then, new polymer electrolytes for conductivity tests are prepared via addition of lithium bis-trifluoromethanesulfonimide. The polymer graft electrolytes exhibit ionic conductivity up to 1.4 × 10-4  S cm-1  at 35 °C. The presence of lignin moderately impacts conductivity at elevated temperature compared to homopolymer PEG. Furthermore, the ionic conductivity of lignin-graft-PEG at ambient temperature is significantly higher than homopolymer PEG precedents.

12.
J Exp Clin Cancer Res ; 39(1): 128, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631394

RESUMO

BACKGROUND: Hepatocellular carcinoma is the third top cause of cancer-related mortalities worldwide. The prognosis of HCC patients remains poor due to rapid progression and high incidence of tumor recurrence. Nicastrin (NCSTN), a core subunit of γ-Secretase, has been reported to play a vital role in tumor progression. However, no study till now has revealed its role in HCC. METHODS: The expression of NCSTN was evaluated by immunohistochemical staining, Western blot, and quantitative real-time PCR. Cell counting kit-8, colony formation and cell cycle assays were used for evaluating cell growth in vitro. Transwell and wound-healing assays were used for evaluating cell migration and invasion capacity. Immunofluorescence, subcellular protein fractionation and co-immunoprecipitation were used for location analysis of ß-catenin. The in vivo functions of NCSTN were illustrated by xenograft tumor models. RESULTS: NCSTN was dramatically overexpressed in HCC compared to normal liver tissues. Elevated NCSTN expression level was significantly correlated to worse overall and recurrence-free survival of HCC patients. Enhanced NCSTN expression promoted HCC cell growth, migration and invasion in vitro and in vivo. Mechanistic investigations showed that NCSTN induced epithelial-mesenchymal transition (EMT) process via upregulation of Zeb1. Subsequently, we revealed that NCSTN facilitated nuclear translocation of ß-catenin, a positive transcriptional regulator of Zeb1. Using Notch and AKT inhibitors, we revealed that NCSTN promoted ß-catenin activation through Notch1 and AKT signaling pathway. NCSTN increased AKT and GSK-3ß phosphorylation by cleavage of Notch1, which decreased GSK-3ß/ß-catenin complex. The inactivation of GSK-3ß inhibited the ß-catenin degradation and promoted nuclear translocation of ß-catenin to initiate transcription of Zeb1, resulting in malignant phenotype. CONCLUSIONS: Our results demonstrated that NCSTN promoted HCC cell growth and metastasis via ß-catenin-mediated upregulation of Zeb1 in a Notch1/AKT dependent manner, suggesting that NCSTN might serve as a potential prognostic marker and therapeutic target for HCC.

13.
Radiat Prot Dosimetry ; 190(2): 200-207, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32685973

RESUMO

This study aimed to explore the diagnosis of urinary calculi through utilisation of low-dose computed tomography (LDCT) with adaptive statistical iterative reconstruction (ASIR). Data from 140 patients that had undergone pathological or operative diagnosis with urinary calculi were analysed. Patients were divided into two groups based on whether they received conventional-dose computed tomography (CDCT) or LDCT, respectively, followed by filtered back projection or ASIR. Average CDCT radiation doses were roughly 4-fold higher than LDCT doses. Despite this difference, there were no significant differences between groups with respect to stone size or location, image quality (P = 0.261), image noise (P = 0.153) and diagnostic efficacy (P = 0.371). LDCT is an effective approach to urinary calculi diagnosis, performing to ASIR while decreasing the effective radiation dose, improving the safety of this procedure.

14.
Int J Biol Sci ; 16(12): 2063-2071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549754

RESUMO

Krüppel-like factor 10 (KLF10) has been identified as an important regulator in carcinogenesis and cancer progression. However, the role of KLF10 in multiply myeloma (MM) development and progression remains unknown. In present study, we found that KLF10 mRNA and protein were down-regulated in MM tissues and cell lines. Notably, KLF10 inhibited cell proliferation, cell cycle progression and promoted apoptosis in vitro and in vivo. Furthermore, we confirmed that KLF10 inhibited ß-catenin nuclear translocation and inhibited PTTG1 transcription. PTTG1 knockdown could mimic the biological effects of KLF10. Moreover, we demonstrated that KLF10 expression was regulated by miR-106b-5p. In MM tissues, miR-106b-5p has an inverse correlation with KLF10 expression. Conclusively, our results demonstrated that KLF10 functions as a tumor suppressor in regulating tumor growth of MM under regulation of miR-106b-5p, supporting its potential therapeutic target for MM.

15.
World Neurosurg ; 141: 149-152, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32544620

RESUMO

BACKGROUND: Acute bilateral internal carotid artery (ICA) occlusion has rarely been reported to exhibit an improvement in prognosis. Herein, we report a case of acute bilateral ICA occlusion presenting with bilateral symmetric cortical and basal-ganglia infarctions that exhibited dramatic improvement after a mechanical thrombectomy. CASE DESCRIPTION: The patient was a 72-year-old man with a history of hypertension who presented with a coma and quadriplegia during sleep and experienced moderate vomiting and diarrhea the day before admission to our hospital. Neurologic examination revealed that the patient was in a coma (National Institutes of Health Stroke Scale 35). A brain computed tomography (CT) scan showed a hypodense lesion in the bilateral frontal cortex. An emergency cerebral angiography demonstrated complete occlusion of the bilateral ICA. Subsequently, a mechanical thrombectomy of the bilateral ICA was successfully performed. At a 3-month follow-up, the patient had residual slight aphasia and quadriparesis (National Institutes of Health Stroke Scale 16). CONCLUSIONS: Bilateral ICA occlusion should be considered if a patient presents with a coma, quadriplegia, and symmetric cortical infarctions. In such a case, a bilateral mechanical thrombectomy may represent a potential treatment for improving the prognosis of the affected patient.

16.
Sci Rep ; 10(1): 10263, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581324

RESUMO

COVID-19 is "public enemy number one" and has placed an enormous burden on health authorities across the world. Given the wide clinical spectrum of COVID-19, understanding the factors that can predict disease severity will be essential since this will help frontline clinical staff to stratify patients with increased confidence. To investigate the diagnostic value of the temporal radiographic changes, and the relationship to disease severity and viral clearance in COVID-19 patients. In this retrospective cohort study, we included 99 patients admitted to the Renmin Hospital of Wuhan University, with laboratory confirmed moderate or severe COVID-19. Temporal radiographic changes and viral clearance were explored using appropriate statistical methods. Radiographic features from HRCT scans included ground-glass opacity, consolidation, air bronchogram, nodular opacities and pleural effusion. The HRCT scores (peak) during disease course in COVID-19 patients with severe pneumonia (median: 24.5) were higher compared to those with pneumonia (median: 10) (p = 3.56 × 10 -12), with more frequency of consolidation (p = 0.025) and air bronchogram (p = 7.50 × 10-6). The median values of days when the peak HRCT scores were reached in pneumonia or severe pneumonia patients were 12 vs. 14, respectively (p = 0.048). Log-rank test and Spearman's Rank-Order correlation suggested temporal radiographic changes as a valuable predictor for viral clearance. In addition, follow up CT scans from 11 pneumonia patients showed full recovery. Given the values of HRCT scores for both disease severity and viral clearance, a standardised HRCT score system for COVID-19 is highly demanded.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Betacoronavirus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos
17.
ACS Appl Mater Interfaces ; 12(26): 29110-29121, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32490661

RESUMO

Existing clinical cell therapies, which rely on the use of biological functionalities of living cells, can be further enhanced by conjugating functional particles to the cells to form cell-particle complexes. Disk-shaped microparticles produced by the top-down microfabrication approach possess unique advantages for this application. However, none of the current mechanisms for conjugating the microfabricated microparticles to the cells are principally applicable to all types of cells with therapeutic potentials. On the other hand, membrane intercalation is a well-established mechanism for attaching fluorescent molecules to living cells or for immobilizing cells on a solid surface. This paper reports a study on conjugating disk-shaped microparticles, referred to as micropatches, to living cells through membrane intercalation for the first time. The procedure for producing the cell-micropatch complexes features an unprecedented integration of microcontact printing of micropatches, end-grafting of linear molecules of octadecyl chain and poly(ethylene glycol) to the printed micropatches, and use of gelatin as a temperature-sensitive sacrificial layer to allow the formation and subsequent release of the cell-micropatch complexes. Complexes composed of mouse neuroblastoma cells were found to be stable in vitro, and the micropatch-bound cells were viable, proliferative, and differentiable. Moreover, complexes composed of four other types of cells were produced. The membrane-intercalation mechanism and the corresponding fabrication technique developed in this study are potentially applicable to a wide range of therapeutic cells and thus promise to be useful for developing new cell therapies enhanced by the disk-shaped microparticles.

18.
ACS Sens ; 5(7): 2198-2204, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32551563

RESUMO

Conventional ion current-based nanopore techniques that identify single molecules are hampered by limitations of providing only the ionic current information. Here, we introduce a silver nanotriangle-based nanopore (diameter < 50 nm) system for detecting molecule translocation using surface-enhanced Raman scattering. Rhodamine 6G is used as a model molecule to study the effect of an electric field (-1 V) on the mass transport. The four DNA bases also show significantly different SERS signals when they are transported into the plasmonic nanopore. The observations suggest that in the electric field, analyte molecules are driven into the nanopipette through the hot spot of the silver nanopore. The plasmonic nanopore shows great potential as a highly sensitive SERS platform for detecting molecule transport and paves the way for single molecule probing.

19.
Front Oncol ; 10: 525, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411593

RESUMO

Background: Liver function is a routine laboratory test prior to curative liver resection. It remains unclear whether the albumin-bilirubin (ALBI) grade and albumin-to-alkaline phosphatase ratio (AAPR) can predict long-term outcomes of surgically treated patients with intrahepatic cholangiocarcinoma (ICC). Methods: This study investigated the correlation between ALBI grade and AAPR with overall survival (OS) after liver resection and then compared their accuracy to the Child-Pugh score. Harrell's concordance index (C-index) and Akaike information criterion (AIC) were used to compare accuracy of models. Results: A total of 620 ICC patients were included, 477 in derivation cohort and 143 for validation. 0.348 was identified as the cutoff value for AAPR after calculating the Youden index. In the derivation cohort, elevated ALBI grade was associated with worse prognosis [hazard ratio (HR): 1.751, 95% confidence interval (CI): 1.329 to 2.306], and a decreased AAPR value was correlated with shorter OS (HR: 1.969, 95% CI: 1.552 to 2.497). Multivariate analysis suggested that the ALBI grade, AAPR, CA19-9, tumor number, and microvascular invasion were independent prognostic predictors for OS. ALBI grade and AAPR showed more accuracy in evaluating OS for surgically treated ICC patients than the Child-Pugh score (C-index: 0.559, 0.600 vs. 0.528; AIC: 3023.84, 3007.73 vs. 3034.66). Our findings were validated in an independent cohort from another clinical center. Conclusions: Importantly, the ALBI grade and AAPR showed greater discriminatory power than the Child-Pugh score in assessing long-term outcomes following hepatectomy for ICC. The AAPR was more accurate than the ALBI grade. It was beneficial to consider the ALBI grade and AAPR as useful surrogate markers to identify patients at risk of poor postoperative outcomes.

20.
Genomics Proteomics Bioinformatics ; 18(1): 26-40, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32413516

RESUMO

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Indóis/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sulfonamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Melanoma/genética , Melanoma/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/metabolismo
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