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1.
Signal Transduct Target Ther ; 6(1): 75, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33619259

RESUMO

The current treatment strategies in advanced malignancies remain limited. Notably, immunotherapies have raised hope for a successful control of these advanced diseases, but their therapeutic responses are suboptimal and vary considerably among individuals. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are often correlated with poor prognosis and therapy resistance, including immunotherapies. Thus, a deeper understanding of the complex roles of TAMs in immunotherapy regulation could provide new insight into the TME. Furthermore, targeting of TAMs is an emerging field of interest due to the hope that these strategies will synergize with current immunotherapies. In this review, we summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition, tumor vaccines and adoptive cell transfer therapies, and discuss the therapeutic potential of targeting TAMs as an adjuvant therapy in tumor immunotherapies.

2.
Cell Prolif ; : e12991, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522656

RESUMO

OBJECTIVE: Premature senescence is related to progerin and involves in endothelial dysfunction and liver diseases. Activating sirtuin 1 (SIRT1) ameliorates liver fibrosis. However, the mechanisms of premature senescence in defenestration of hepatic sinusoidal endothelial cells (HSECs) and how SIRT1 affects HSECs fenestrae remain elusive. METHODS: We employed the CCl4 -induced liver fibrogenesis rat models and cultured primary HSECs in vitro, administered with the SIRT1-adenovirus vector, the activator of SIRT1 and knockdown NOX2. We measured the activity of senescence-associated ß-galactosidase (SA-ß-gal) in HSECs. Meanwhile, the protein expression of SIRT1, NOX2, progerin, Lamin A/C, Ac p53 K381 and total p53 was detected by Western blot, co-immunoprecipitation and immunofluorescence. RESULTS: In vivo, premature senescence was triggered by oxidative stress during CCl4 -induced HSECs defenestration and liver fibrogenesis, whereas overexpressing SIRT1 with adenovirus vector lessened premature senescence to relieve CCl4 -induced HSECs defenestration and liver fibrosis. In vitro, HSECs fenestrae disappeared, with emerging progerin-associated premature senescence; these effects were aggravated by H2 O2 . Nevertheless, knockdown of NOX2, activation of SIRT1 with resveratrol and SIRT1-adenovirus vector inhibited progerin-associated premature senescence to maintain fenestrae through deacetylating p53. Furthermore, more Ac p53 K381 and progerin co-localized with the abnormal accumulation of actin filament (F-actin) in the nuclear envelope of H2 O2 -treated HSECs; in contrast, these effects were rescued by overexpressing SIRT1. CONCLUSION: SIRT1-mediated deacetylation maintains HSECs fenestrae and attenuates liver fibrogenesis through inhibiting oxidative stress-induced premature senescence.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33470042

RESUMO

Discovering the underlying reason for Li anode failure is a critical step towards applications of lithium metal batteries (LMBs). In this work, we conduct deuterium-oxide (D2 O) titration experiments in a novel on-line gas analysis mass spectrometry (MS) system, to determine the content of metallic Li and lithium hydride (LiH) in cycled Li anodes disassembled from practical LiCoO2 /Li LMBs. The practical cell is comprised of ultrathin Li anode (50 µm), high loading LiCoO2 (17 mg cm-2 , 2.805 mAh cm-2 ) and different formulated electrolytes. Our results suggest that the amount of LiH accumulation is negatively correlated with cyclability of practical LMBs. More importantly, we reveal a temperature sensitive equilibrium (Li + 1/2 H2 ⇌ LiH) governing formation and decomposition process of LiH at Li anode. We believe that the unusual understanding provided by this study will draw forth more insightful efforts to realize efficient Li protection and the ultimate applications of "holy grail" LMBs.

4.
Mol Diagn Ther ; 25(1): 29-40, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433895

RESUMO

The ubiquitin proteasome system (UPS) is a highly conserved way to regulate protein turnover in cells. The UPS hydrolyzes and destroys variant or misfolded proteins and finely regulates proteins involved in differentiation, apoptosis, and other biological processes. This system is a key regulatory factor in the proliferation, differentiation, and collagen secretion of skin fibroblasts. E3 ubiquitin protein ligases Parkin and NEDD4 regulate multiple signaling pathways in keloid. Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) binding with deubiquitinase USP10 can induce p53 destabilization and promote keloid-derived fibroblast proliferation. The UPS participates in the occurrence and development of hypertrophic scars by regulating the transforming growth factor (TGF)-ß/Smad signaling pathway. An initial study suggests that TNFα-induced protein 3 (TNFAIP3) polymorphisms may be significantly associated with scleroderma susceptibility in individuals of Caucasian descent. Sumoylation and multiple ubiquitin ligases, including Smurfs, UFD2, and KLHL42, play vital roles in scleroderma by targeting the TGF-ß/Smad signaling pathway. In the future, drugs targeting E3 ligases and deubiquitinating enzymes have great potential for the treatment of skin fibrosis.

5.
Mol Med Rep ; 23(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33236153

RESUMO

Although long non­coding RNAs (lncRNAs) have been implicated in various human cancer types, the role of lncRNA ezrin antisense RNA 1 (EZR­AS1) in cutaneous squamous cell carcinoma (cSCC) remains unclear. The present study aimed to investigate the effect of lncRNAEZR­AS1 on cSCC and identify the underlying molecular mechanisms. EZR­AS1 expression was measured in cSCC tissue and cells detected using reverse transcription­quantitative PCR. Gain­of­function assays were performed in A431 cells, which have a relatively low expression of EZR­AS1, while loss­of­function assays were performed in SCC13 and SCL­1 colon cancer cells, which have a relatively high expression of EZR­AS1. Cell viability, proliferation, migration, invasion and apoptosis were assessed using MTT, plate cloning, wound healing, Transwell and flow cytometry assays, respectively. EZR­AS1 mRNA expression levels were significantly upregulated in cSCC tissues and cells compared with adjacent healthy tissues and HaCaT cells, respectively. Compared with the small interfering RNA (si)­negative control (NC) group, si­EZR­AS1 significantly inhibited SCC13 and SCL­1 cell proliferation, migration and invasion, but promoted cell apoptosis. By contrast, compared with the pc­NC group, EZR­AS1 overexpression significantly enhanced A431 cell proliferation, migration and invasion, but inhibited cell apoptosis. Moreover, focal adhesion kinase (FAK) was identified as a target of EZR­AS1, and EZR­AS1 knockdown significantly decreased FAK expression compared with the si­NC group. Moreover, EZR­AS1 knockdown significantly downregulated the protein expression levels of phosphorylated (p)­PI3K/PI3K and p­AKT/AKT in cSCC cells compared with the si­NC group. The PI3K agonist 740Y­P significantly reversed si­EZR­AS1­mediated effects on SCC13 and SCL­1 cell proliferation, migration, invasion and apoptosis. In conclusion, the present study demonstrated that si­EZR­AS1 inhibited cSCC cell proliferation, migration and invasion, and promoted cell apoptosis, potentially via regulating the PI3K/AKT signaling pathway. Therefore, the present study provided novel insights into the diagnosis and treatment of cSCC.

6.
Phytochemistry ; 182: 112597, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33341030

RESUMO

Seven pairs of undescribed enantiomeric bis-coumarins, (±)-dievodialetins A-G, were separated from the roots of Evodia lepta Merr. Two coumarin nuclei were linked via a 1,4-dimethyl4-vinylcyclohexene moiety in (±)-dievodialetins C-G. The structures of the undescribed compounds, including their absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. In the biosynthetic pathways, these bis-coumarins were presumably derived from the precursors demethylsuberosin and 3-(3-methylbut-2-enyl)umbelliferone via a [4 + 2] Diels-Alder reaction. Besides, all compounds exhibited neuroprotective effects by inhibiting acetylcholinesterase (AChE) activity with IC50 values ranging from 7.3 to 12.1 nM and they also suppressed oxidative stress (MDA and SOD) and neuroinflammation (IL-1ß and IL-6).


Assuntos
Evodia , Rutaceae , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Cumarínicos/farmacologia , Estrutura Molecular , Raízes de Plantas/metabolismo , Rutaceae/metabolismo
7.
Am Heart J ; 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33264607

RESUMO

BACKGROUND: Post-discharge mortality following hospitalization for heart failure with reduced ejection fraction (HFrEF) has remained high and unchanged over the past two decades, despite effective therapies for HFrEF. We aimed to explore whether these patterns could in part be explained by changes in longitudinal risk profile and HF severity over time. METHODS: Among patients hospitalized for HF in the GWTG-HF registry from 1/2005 to 12/2018 with available data, we evaluated GWTG-HF and ADHERE risk scores, observing in-hospital mortality per-year. The risk profiles and outcomes were described overall and by subgroups based on ejection fraction (EF), diabetes mellitus (DM), sex, and age. RESULTS: Overall, 335,735 patients were included (50% HFrEF, 46% DM, 48% female, mean age 74 years). In-hospital mortality increased by 2.0% per year from 2005-2018. There was no significant change in mean GWTG-HF risk score overall or when stratified by EF groups (p=0.46 HFrEF, p=0.26 HF mid-range EF [HFmrEF], and p=0.72 HF preserved EF [HFpEF]), age, sex, or presence of DM. The observed/expected ratio based on the GWTG-HF risk score was 0.93 (0.91-0.96), 0.83 (0.77-0.90), 0.92 (0.89-95) for HFrEF, HFmrEF, and HFpEF, respectively. Similar findings were seen when risk was assessed using ADHERE risk score. CONCLUSIONS: There were no significant changes in average risk profiles among hospitalized HF patients over the study duration. These data do not support the notion that worsening risk profile explains the lack of improved outcomes despite therapeutic advances, underscoring the importance of aggressive implementation of guideline-recommended therapies and investigation of novel treatments.

9.
Aging (Albany NY) ; 12(21): 21660-21673, 2020 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-33168782

RESUMO

Effective therapies for non-alcoholic steatohepatitis (NASH) are urgently needed. We investigated the effect of human mesenchymal stem cells (hMSCs) on the intestinal flora in NASH treatment. We isolated the hMSCs from the umbilical cords and divided male C57BL/6 mice into three groups, namely, chow, methionine-choline-deficient (MCD), and MCD+hMSCs. After collecting the feces and liver of the mice, we evaluated the histological changes in the liver and measured the inflammatory and fibrogenesis cytokines. Fecal microbiome and metabolome were analyzed using 16S rRNA gene sequencing analyses. The hMSCs treatment could alleviate hepatic steatosis, inflammation and fibrosis induced by MCD diet. It could also reverse the microbiome and metabolome disorders in the NASH model. Correlation analysis of the interaction among bacteria amplified the effects of the bacteria in host. In conclusion, hMSCs treatment could improve NASH-related lesions and reverse gut microbiome and metabolome disorder in NASH.

10.
Vaccine ; 38(50): 7970-7976, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33129609

RESUMO

BACKGROUND: Multiple Anthrax vaccines are licensed or in development for post-exposure prophylaxis in individuals 18 to 65 years of age. No information exists on anthrax vaccines in populations over the age of 65. It is critical that we assess the capacity of anthrax vaccines to generate a protective immune response in older individuals. In this study, we compared BioThrax® to a formulation containing a CpG adjuvant (AV7909). METHODS: We conducted a Phase 2 clinical study to evaluate safety and immunogenicity of three vaccination schedules of the AV7909 vaccine candidate and one vaccination schedule of BioThrax® vaccine in adults over 65 years of age. A total of 305 subjects were enrolled to assess safety and immunogenicity by seroprotection rates, toxin neutralizing antibody titers, and anti-Protective Antigen ELISA titers. RESULTS: Compared to BioThrax, AV7909 elicited a more robust immune response in older subjects, especially with three doses of AV7909 at Days 1, 15, and 29, or two doses at Days 1 and 29. These trends were true with both seroprotection rates as defined by the percentage of subjects with 50 percent neutralization factors greater than 0.56, and geometric mean antibody titers. The responses to both AV7909 and BioThax were lower in older subjects compared to those aged 18-50. CONCLUSION: The immunogenicity data suggest that the CpG adjuvant in the AV7909 vaccine helps to elicit a more robust immune response in subjects over the age of 65. Alternative dosing strategies may be considered in this population given the high seroprotection rates with Day 1 and 29, or Day 1, 15, and 29 regimens. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03518125.

11.
Front Mol Neurosci ; 13: 605722, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192302

RESUMO

[This corrects the article DOI: 10.3389/fnmol.2018.00155.].

12.
J Microbiol ; 58(12): 1027-1036, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33095389

RESUMO

The Gram-positive bacterium Enterococcus faecalis is currently one of the major pathogens of nosocomial infections. The lifestyle of E. faecalis relies primarily on its remarkable capacity to face and survive in harsh environmental conditions. Toxin-antitoxin (TA) systems have been linked to the growth control of bacteria in response to adverse environments but have rarely been reported in Enterococcus. Three functional type II TA systems were identified among the 10 putative TA systems encoded by E. faecalis ATCC29212. These toxin genes have conserved domains homologous to MazF (DR75_1948) and ImmA/IrrE family metallo-endopeptidases (DR75_1673 and DR75_2160). Overexpression of toxin genes could inhibit the growth of Escherichia coli. However, the toxin DR75_1673 could not inhibit bacterial growth, and the bacteriostatic effect occurred only when it was coexpressed with the antitoxin DR75_1672. DR75_1948-DR75_1949 and DR75_160-DR75_2161 could maintain the stable inheritance of the unstable plasmid pLMO12102 in E. coli. Moreover, the transcription levels of these TAs showed significant differences when cultivated under normal conditions and with different temperatures, antibiotics, anaerobic agents and H2O2. When DR75_2161 was knocked out, the growth of the mutant strain at high temperature and oxidative stress was limited. The experimental characterization of these TAs loci might be helpful to investigate the key roles of type II TA systems in the physiology and environmental stress responses of Enterococcus.

13.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(10): 1500-1506, 2020 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-33118516

RESUMO

OBJECTIVE: To propose a probabilistic neural network classification method optimized by simulated annealing algorithm (SA-PNN) to discriminate lung cancer and adjacent normal tissues based on permittivity. METHODS: The permittivity of lung tumors and the adjacent normal tissues was measured by an open-ended coaxial probe, and the statistical dependency (SD) algorithm was used for frequency screening.The permittivity associated with the selected frequency points was taken as the characteristic variable, and SA-PNN was used to discriminate lung cancer and the adjacent normal tissues. RESULTS: Three frequency points, namely 984 MHz, 2724 MHz and 2723 MHz, were selected by SD algorithm.SA-PNN was used to discriminate 200 samples with the permittivity at the 3 frequency points as the characteristic variable.After 10-fold cross-validation, the final discrimination accuracy was 92.50%, the sensitivity was 90.65%, and the specificity was 94.62%. CONCLUSIONS: Compared with the traditional probabilistic neural network, BP neural network, RBF neural network and the classification discriminant analysis function (Classify) in MATLAB, the proposed SA-PNN has higher accuracy, sensitivity and specificity for discriminating lung cancer and the adjacent normal tissues based on permittivity.


Assuntos
Neoplasias Pulmonares , Redes Neurais de Computação , Algoritmos , Humanos , Neoplasias Pulmonares/diagnóstico , Sensibilidade e Especificidade
14.
Am J Cardiol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068540

RESUMO

The purpose of this analysis was to assess implantable cardioverter-defibrillator (ICD) utilization and its association with mortality among patients ≥65 years of age after coronary revascularization. Patients in the National Cardiovascular Database Registry Chest Pain-Myocardial Infarction (MI) Registry who presented with MI from January 2, 2009 to December 31, 2016, had a left ventricular ejection fraction ≤35% and underwent in-hospital revascularization (10,014 percutaneous coronary intervention (PCI) and 1,647 coronary artery bypass grafting (CABG)) were linked with Medicare claims to determine rates of 1-year ICD implantation. The association between ICD implantation and 2-year mortality was assessed. Of 11,661 included patients, an ICD was implanted in 1,234 (10.6%) within 1 year of revascularization (1,063 (10.6%) PCI and 171 (10.4%) CABG). Among PCI-treated patients, in-hospital ventricular arrhythmia (adjusted hazard ratio [aHR] 1.60, 95% confidence interval [CI] 1.34 to 1.92), 2-week cardiology follow-up (aHR 1.48, 95% CI 1.29 to 1.70), readmission for heart failure (aHR 3.21, 95% CI 2.73 to 3.79), and readmission for MI (aHR 2.18, 95% CI 1.66 to 2.85) were positively associated with ICD implantation. Among CABG-treated patients, in-hospital ventricular arrhythmia (aHR 2.33, 95% CI 1.39 to 3.91), and heart failure readmission (aHR 3.14, 95% CI 1.96 to 5.04) were positively associated with ICD implantation. Women were less likely to receive an ICD, regardless of the revascularization strategy. ICD implantation was associated with lower 2-year all-cause mortality (aHR 0.74, 95% CI 0.63 to 0.86). In conclusion, only 1 in 10 Medicare patients with low ejection fraction received an ICD within 1 year after revascularization. Contact with the healthcare system after discharge was associated with higher likelihood of ICD implantation. ICD implantation was associated with lower mortality following revascularization for MI.

15.
Sci Rep ; 10(1): 17249, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057069

RESUMO

The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers.

16.
Front Mol Neurosci ; 13: 554547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013320

RESUMO

Epilepsy is a chronic brain dysfunction induced by an abnormal neuronal discharge that is caused by complicated psychopathologies. Recently, accumulating studies have revealed a close relationship between inflammation and epilepsy. Specifically, microglia and astrocytes are important inflammatory cells in the central nervous system (CNS) that have been proven to be related to the pathogenesis and development of epilepsy. Additionally, interleukin 4 (IL-4) is an anti-inflammatory factor that can regulate microglia and astrocytes in many aspects. This review article focuses on the regulatory role of IL-4 in the pathological changes of glial cells related to epilepsy. We additionally propose that IL-4 may play a protective role in epileptogenesis and suggest that IL-4 may be a novel therapeutic target for the treatment of epilepsy.

17.
Biomed Res Int ; 2020: 3120458, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029500

RESUMO

Background: Osteonecrosis of the femoral head (ONFH) is a challenge for surgeons and is still without effective treatment method. This study is aimed at evaluating the combined pharmacotherapy with alendronate and desferoxamine for preventing glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) and evaluating the efficacy of the combined medicine in regulating the bone resorption and bone regeneration. Materials and Methods: Thirty-six rats were randomly assigned to three groups: group A received alendronate and desferoxamine (n = 12), group B received alendronate only (n = 12), and group C acted as the control group received placebo (n = 12). All rats induced the GIOFH using methylprednisolone combined with lipopolysaccharide. Eight weeks later, all rats were killed and their tissues were subjected to radiographic and histological analyses. Results: According to the results, alendronate administration improved the trabecular thickness and separation in micro-CT analysis but had no significant evidence in increasing the bone area and decreasing the ratio of osteocyte lacunae in histological analysis when compared with the control group. Meanwhile, the alendronate group had more OCs, but less OCN and VEGF levels along with decreased p-AKT, HIF-1α, RANKL, and NFATc1 expressions than the control group. For comparison, alendronate combined with DFO further improved the bone volume, trabecular number, trabecular separation, and trabecular thickness with lower ratio of osteocyte lacunae and OC number, higher expression of OCN and VEGF and upregulated signal factors of HIF-1α and ß-catenin, and decreased RANKL and NFATc1. Conclusion: Combined pharmacotherapy with alendronate and desferoxamine provide significant effects in regulating the bone resorption and bone regeneration for preventing GIOFN.

18.
Onco Targets Ther ; 13: 9245-9255, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982311

RESUMO

Introduction: Owing to its involvement in both the initiation and progression of various cancers, aberrant circular RNA (circRNA) expression has been researched extensively in the recent times. In the present study, we aim to investigate the effect of a novel circRNA has_circ_0025933 (circNELL2) in the progression of esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sanger sequencing and the detection of circNELL2 level after RNase R or actinomycin D treatment were performed to identify the existence of cirNELL2 in ESCC cells. WST, EDU staining and colony-formation assay were used to assess the proliferation while transwell assay was used to evaluate the migration of ESCC cells. Luciferase assay, RNA pull down and the FISH assay were performed to verify the interaction between circNELL2 and miR-127-5p as well as miR-127-5p and CDC6. Xenograft model was carried out to evaluate the effect of circNELL2 in vivo. Results: circNELL2 was proved to exist in ESCC cells. The up-regulated expression of circNELL2 in the clinical ESCC specimens was also verified. Next, function studies suggested that circNELL2 knockdown inhibited the proliferation of ESCC cells in vitro and in vivo, while circNELL2 overexpression promotes that of ESCC cells. Besides, this study mechanically predicted and verified the target miR of circNELL2, which is miR-127-5p. It was found that miR-127-5p was capable of reversing the effect of circNELL2 on ESCC cells. Moreover, miR-127-5p was also found to target CDC6 to participate in the regulation of cell phenotype. Discussion: circNELL2 promoted the progression of ESCC cells via sponging miR-127-5p, and it has the potential to serve as a novel prognostic and therapeutic target for ESCC.

20.
J Cancer ; 11(17): 5069-5077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742454

RESUMO

The heterogeneity of hepatocellular carcinoma (HCC) commonly leads to therapeutic failure of HCC. Cytokeratin 19 (CK19) is well acknowledged as a biliary/progenitor cell marker and a marker of tumor stem cell. CK19-positive HCCs demonstrate aggressive behaviors and poor outcomes which including worse overall survival and early tumor recurrence after hepatectomy and liver transplantation. CK19-positive HCCs are resistant to chemotherapies as well as local treatment. This subset of HCC is thought to derive from liver progenitor cells and can be induced by extracellular stimulation such as hypoxia. Besides being a stemness marker, CK19 plays an important role in promoting malignant property of HCC. The regulatory network associated with CK19 expression has been summarized that extracellular stimulations which transmit into cytoplasm through signal transduction pathways (TGF-ß, MAKP/JNK and MEK-ERK1/2), further induce important nuclear transcriptional factors (SALL4, AP1, SP1) to activate CK19 promoter. Novel noncoding RNAs are also involved in the regulation of CK19 expression. TGFßR1 becomes a therapeutic target for CK19-positive HCC. In conclusion, CK19 can be a potential biomarker for predicting poor prognosis after surgical and adjuvant therapies. CK19-pisitive HCCs exhibit distinctive molecular profiling, should be diagnosed and treated as a separate subtype of HCCs.

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