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1.
Phys Rev E ; 107(6-1): 064108, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37464630

RESUMO

With large-scale Monte Carlo simulations, we investigate the nonsteady relaxation at the dynamic depinning transition in the two-dimensional Gaussian random-field Ising model. The dynamic scaling behavior is carefully analyzed, and the transition fields as well as static and dynamic exponents are accurately determined based on the short-time dynamic scaling form. Different from the usual assumption, two distinguished growth processes of spatial correlation lengths for the velocity and height of the domain wall are found. Thus, the universality class of the depinning transition is established, which significantly differs from that of the quenched disorder equation but agrees with that of the recent experiment as well as other simulations works. Under the influence of the mesoscopic time regime, the crossover from the second-order phase transition to the first-order one is confirmed in the weak-disorder regime, yielding an abnormal disorder-dependent nature of the criticality.

2.
Acta Biomater ; 162: 85-97, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36948328

RESUMO

The therapeutic effects of photothermal therapy (PTT) are dependent on the photothermal conversion efficiency of photothermal agents (PTAs) in tumors and the subsequent activation of the antitumor immune system. However, the insufficient tumor accumulation of current PTAs and the inevitable recruitment of tumor-associated macrophages (TAMs) could further compromise the antitumor activities of PTT. To address these issues, a biomimetic photothermal nanoplatform Au@Fe-PM is developed for the targeted remodeling of TAMs, which promotes the antitumor immunity of PTT. Au nanorods with second near-infrared (NIR-II) absorptions are fabricated to serve as PTAs to induce immunogenic cell death in tumor cells. The ferric hydroxide shell coated on Au nanorods can release iron ions to repolarize M2-like TAMs into the tumoricidal M1 phenotype via P38 and STAT1-mediated signaling pathways. Moreover, the surface decoration of platelet membranes endows biomimetic nanoplatform with enhanced tumor targeting ability for precise tumor ablation and TAM regulation. Consequently, Au@Fe-PM under NIR-II laser irradiation exhibits significantly higher inhibitory effects in a poor immunogenic 4T1 tumor-bearing mouse model with a 50% complete remission rate compared to conventional PTT (0%). By simultaneously reversing the immunosuppressive tumor microenvironment, this biomimetic nanoplatform offers a promising strategy for enhancing the antitumor efficacy of PTT. STATEMENT OF SIGNIFICANCE: The therapeutic effects of current photothermal therapy (PTT) are hindered by the insufficient tumor accumulation of conventional photothermal agents and the recruitment of immunosuppressive tumor-associated macrophages (TAMs) after PTT. Herein, we report a biomimetic iron-based second near-infrared (NIR-II) photothermal nanoplatform (Au@Fe-PM) for targeted TAMs reprogramming and NIR-II mediated anti-tumor immunity. Au@Fe-PM can actively target the tumor site with the help of surface-decorated platelet membranes. Meanwhile, iron ions would be released from Au@Fe-PM in acidic lysosomes to reprogram TAMs into tumoricidal M1-like macrophages, which promotes the antitumor responses elicited by NIR-II PTT, thereby contributing to remarkable tumor inhibitory effects, with 50% higher complete remission rate than that of conventional PTT.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Fototerapia , Macrófagos Associados a Tumor/patologia , Biomimética , Neoplasias/patologia , Ferro , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente Tumoral
3.
Cell Death Dis ; 13(12): 1076, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36575197

RESUMO

The function and underlying mechanisms of p50 in the regulation of protein expression is much less studied because of its lacking of transactivation domain. In this study, we discovered a novel function of p50 in its stabilization of hypoxia-inducible factor 1α (HIF-1α) protein under the condition of cells exposed to arsenic exposure. In p50-deficient (p50-/-) cells, the HIF-1α protein expression was impaired upon arsenic exposure, and such defect could be rescued by reconstitutional expression of p50. Mechanistic study revealed that the inhibition of autophagy-related gene 7 (ATG7)-dependent autophagy was in charge of p50-mediated HIF-1α protein stabilization following arsenic exposure. Moreover, p50 deletion promoted nucleolin (NCL) protein translation to enhance ATG7 mRNA transcription via directly binding transcription factor Sp1 mRNA and increase its stability. We further discovered that p50-mediated miR-494 upregulation gave rise to the inhibition of p50-mediated NCL translation by interacting with its 3'-UTR. These novel findings provide a great insight into the understanding of biomedical significance of p50 protein in arsenite-associated disease development and therapy.


Assuntos
Arsênio , Transcrição Gênica , Regulação para Cima , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Autofagia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
4.
Cell Death Dis ; 13(8): 753, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045117

RESUMO

Although our previous studies have identified that isorhapontigenin (ISO) is able to initiate autophagy in human bladder cancer (BC) cells by activating JNK/C-Jun/SESN2 axis and possesses an inhibitory effect on BC cell growth, association of autophagy directly with inhibition of BC invasion has never been explored. Also, upstream cascade responsible for ISO activating JNK remains unknown. Thus, we explored both important questions in the current study and discovered that ISO treatment initiated RAC1 protein translation, and its downstream kinase MKK7/JNK phosphorylation/activation, and in turn promoted autophagic responses in human BC cells. Inhibition of autophagy abolished ISO inhibition of BC invasion, revealing that autophagy inhibition was crucial for ISO inhibition of BC invasion. Consistently, knockout of RAC1 also attenuated induction of autophagy and inhibition of BC invasion by ISO treatment. Mechanistic studies showed that upregulation of RAC1 translation was due to ISO inhibition of miR-365a transcription, which reduced miR-365a binding to the 3'-UTR of RAC1 mRNA. Further study indicated that inhibition of miR-365a transcription was caused by downregulation of its transcription factor SOX2, while ISO-promoted Dicer protein translation increased miR-145 maturation, and consequently downregulating SOX2 expression. These findings not only provide a novel insight into the understanding association of autophagy induction with BC invasion inhibition by ISO, but also identify an upstream regulatory cascade, Dicer/miR145/SOX2/miR365a/RAC1, leading to MKK7/JNKs activation and autophagy induction.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Regiões 3' não Traduzidas , Autofagia/genética , Linhagem Celular Tumoral , RNA Helicases DEAD-box , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Fosforilação , Biossíntese de Proteínas , Ribonuclease III , Fatores de Transcrição SOXB1/metabolismo , Sestrinas , Estilbenos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
5.
Theranostics ; 12(9): 4250-4268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35673566

RESUMO

Background: Despite their outstanding properties in high surface-to-volume ratio and deep penetration, the application of ultrasmall nanoparticles for tumor theranostics remains limited because of their dissatisfied targeting performance and short blood circulation lifetime. Various synthetic materials with complex structures have been prepared as a multifunctional platform for loading ultrasmall nanoparticles. However, their use in nanomedicine is restricted because of unknown metabolic processes and potential physiological toxicity. Therefore, versatile and biocompatible nanoplatforms need to be designed through a simple yet effective method for realizing specific delivery and responsible release of ultrasmall nanoparticles. Methods: Iron-gallic acid coordination polymer nanodots (FeCNDs) exhibits outstanding photothermal ability and Fenton catalytic performance, which can be applied for tumor inhibition via hyperthermia and reactive oxygen species. A pH-responsive platelet-based hybrid membrane (pH-HCM) was prepared via co-extrusion and acted as a safe nanoplatform to load FeCNDs (pH-HCM@FeCNDs). Subsequently, their responsive performance and penetration ability were valued considering the multicellular sphere (MCS) model in an acidic or neutral environment. Thereafter, in vivo fluorescence image was performed to assess targeting capability of pH-HCM@FeCNDs. Finally, the corresponding antitumor and antimetastatic effects on orthotropic breast cancer were investigated. Results: In 4T1 MCS model, pH-HCM@FeCNDs group exhibited higher penetration efficiency (72.84%) than its non-responsive counterparts (17.77%) under an acidic environment. Moreover, the fluorescence intensity in pH-HCM@FeCNDs group was 3.18 times higher than that in group without targeting performance in the in vivo fluorescence image experiment. Finally, through in vivo experiments, pH-HCM@FeCNDs was confirmed to exhibit the best antitumor effect (90.33% tumor reduction) and antimetastatic effects (only 0.29% tumor coverage) on orthotropic breast cancer. Conclusions: Hybrid cell membrane was an ideal nanoplatform to deliver nanodots because of its good responsibility, satisfactory targeting ability, and excellent biocompatibility. Consequently, this study provides novel insights into the delivery and release of nanodots in a simple but effect method.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Nanopartículas , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas/química
6.
Cancer Cell Int ; 21(1): 636, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844614

RESUMO

BACKGROUND: Circular RNAs (circRNAs), which are endogenous non-coding RNAs, are associated with various biological processes including development, homeostatic maintenance, and pathological responses. Accumulating evidence has implicated non-coding RNAs in cancer progression, and the role of circRNAs in particular has drawn wide attention. However, circRNA expression patterns and functions in hepatocellular carcinoma (HCC) remain poorly understood. METHODS: CircRNA sequencing was performed to screen differentially expressed circRNAs in HCC. Northern blotting, quantitative real-time polymerase chain reaction, nucleocytoplasmic fractionation, and fluorescence in situ hybridization analyses were conducted to evaluate the expression and localization of circSLC7A11 in HCC tissues and cells. CircSLC7A11 expression levels were modified in cultured HCC cell lines to explore the association between the expression of circSLC7A11 and the malignant behavior of these cells using several cell-based assays. The modified cells were implanted into immunocompetent nude mice to assess tumor growth and metastasis in vivo. We applied bioinformatics methods, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays to explore the mechanisms of circSLC7A11 in HCC. RESULTS: CircSLC7A11 (hsa_circ_0070975) was conserved and dramatically overexpressed in HCC tissues and cells. HCC patients showing high circSLC7A11 expression had worse prognoses. Our in vitro and in vivo experiments showed that circSLC7A11 markedly accelerated HCC progression and metastasis through the circSLC7A11/miR-330-3p/CDK1 axis. CONCLUSIONS: The acceleration of HCC progression and metastasis by circSLC7A11 through the circSLC7A11/miR-330-3p/CDK1 axis suggests that circSLC7A11 is a potential novel diagnostic and therapeutic target for HCC treatment.

7.
Front Endocrinol (Lausanne) ; 12: 613755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746899

RESUMO

Background: The American Joint Committee on Cancer (AJCC) staging for pancreatic neuroendocrine neoplasms (PanNENs) based on the number of positive lymph nodes (PLNs) is the most widely accepted nodal staging system. New nodal staging schemes that take both the number of PLNs and the number of examined lymph nodes into consideration have emerged as useful prognostic tools. The aim of the current study was to determine the most effective nodal staging system, among the 8th edition AJCC N staging (or PLN staging), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS), for predicting the cause-specific survival of patients with PanNENs. Methods: The clinicopathological and prognostic data of 2,295 patients from the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with PanNENs between 1988 and 2015, were reviewed retrospectively. Results: A multivariate analysis identified PLN and LNR staging as independent prognostic factors, but not LODDS. The PLN staging exhibited higher C-index and area under the curve values than those of the LNR and LODDS, indicating better predictive discriminatory capacity. No significant difference in the survival of patients was observed within the same PLN staging subgroup according to the number (high or low) of examined lymph nodes. In contrast, intra-group heterogeneity was seen with use of LNR and LODDS staging, due to overestimation of the risk of insufficient examined lymph nodes, and LODDS failed to stratify patients without lymph nodes metastasis into different risk groups. Conclusions: The PLN staging is more reliable than LNR and LODDS staging for predicting the cause-specific survival of PanNENs.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , História do Século XX , História do Século XXI , Humanos , Razão entre Linfonodos , Metástase Linfática/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Razão de Chances , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Programa de SEER
8.
J Cancer ; 12(5): 1284-1294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531974

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and represents a classic paradigm of inflammation-related cancer. Various inflammation-related risk factors jointly contribute to the development of chronic inflammation in the liver. Chronic inflammation, in turn, leads to continuous cycles of destruction-regeneration in the liver, contributing to HCC development and progression. Tumor associated macrophages are abundant in the tumor microenvironment of HCC, promoting chronic inflammation and HCC progression. Hence, better understanding of the mechanism by which tumor associated macrophages contribute to the pathogenesis of HCC would allow for the development of novel macrophage-targeting immunotherapies. This review summarizes the current knowledge regarding the mechanisms by which macrophages promote HCC development and progression, as well as information from ongoing therapies and clinical trials assessing the efficacy of macrophage-modulating therapies in HCC patients.

9.
J Cancer ; 12(6): 1770-1778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613766

RESUMO

Background: Portal vein embolization (PVE) is performed before major liver resection to increase liver volume remnant, controversy remains on the adverse effect of PVE on liver tumor patients. The current study highlighted the effect of PVE on the degree of hypertrophy of future liver remnant (FLR) and summarized PVE-related complications, aiming to provide a guideline for surgeons. Methods: A search of current published studies on PVE was performed. Meta-analysis was conducted to assess the effect of PVE on hypertrophy of FLR and summarized PVE-related complications. Results: 26 studies including 2335 patients were enrolled in the meta-analysis. All enrolled studies reported data regarding FLR hypertrophy rate, pooled effect size (ES) for FLR hypertrophy rate using a fixed-effect model was 0.105 (95%CI: 0.094-0.117, p=0.000), indicating PVE is favored in inducing FLR hypertrophy. Metatrim method indicated no obvious evidence of publication bias in the present meta-analysis. 247 (10.6%) patients exhibited PVE-related complications, receiving expectant treatment without affecting planned liver resection. Total 1782 patients (76%) underwent a subsequent liver resection after PVE, which is an encouraging result comparing with traditional resection rate in liver tumor patients. Conclusions: PVE is a safe and effective procedure with a low occurrence of related complications for inducing sufficient hypertrophy of FLR in liver tumor patients, which could elevate the resection rate of liver tumor patients. Careful patient cohort selection is crucial to avoid overuse of PVE in technically resectable patients. Further multiple central clinical trials are conducive to select optimal patient cohorts and provide a guideline for surgeons.

10.
Medicine (Baltimore) ; 99(52): e23610, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350736

RESUMO

RATIONALE: Lymphoepithelioma-like carcinoma (LELC) is a rare malignant tumor that can occur in many areas of the body. The pathogenesis of LELC remains unknown, but Epstein-Barr virus (EBV) has been shown to be strongly correlated with LELC at several anatomic sites, including the lungs and thymus. To the best of our knowledge, EBV-associated LELC has never been reported in both the posterior mediastinum and liver. Herein, we report the case of a 41-year-old female diagnosed with LELC in both the posterior mediastinum and liver and discuss whether it is beneficial to perform surgery on advanced LELC when resectable metastases are found. PATIENT CONCERNS: The patient was a 41-year-old woman who had been suffering from intermittent pain in the upper right quadrant for 3 months without obvious cause and was admitted to our hospital with occasional nausea without vomiting. DIAGNOSIS: Her cancer antigen 125 and cytokeratin 19 fragment levels were elevated, whereas alpha-fetoprotein and alanine aminotransferase were normal. Computed tomography (CT) and magnetic resonance imaging revealed a mass in the S6 segment of the liver. Whole-body positron emission tomography/computed tomography (PET/CT) revealed a 3.2-cm mass in the posterior mediastinum and a 6.7-cm mass on the right side of the liver. We made a diagnosis of LELC based on the histological and immunohistochemical findings of specimens obtained by operation. However, it was difficult to determine the primary origin of the tumor. INTERVENTIONS: The patient underwent mediastinal tumor resection, hepatectomy, and diaphragmatic repair. Thereafter, she was administered paclitaxel and cisplatin as adjuvant chemotherapy. OUTCOMES: The postoperative course was uneventful, and the patient was discharged 10 days later. Although she was administered paclitaxel and cisplatin as adjuvant chemotherapy, we noted recurrence during the 4-month follow-up examination. Then, the patient passed away 5 months after surgery. LESSONS: We present the first case of LELC found in both the posterior mediastinum and liver and describe the functionality of PET/CT for finding occult carcinomas and identifying their primary tumor origin. Additional studies are urgently needed to discover whether it is beneficial to perform surgery on advanced LELC when resectable metastases are revealed by PET/CT.


Assuntos
Carcinoma/cirurgia , Carcinoma/virologia , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/virologia , Adulto , Feminino , Humanos
11.
World J Gastroenterol ; 26(40): 6195-6206, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33177793

RESUMO

Gastrointestinal stromal tumors (GIST), which is the most common mesenchymal tumor of the digestive tract, account for 1%-3% of gastrointestinal tumors. Primary stromal tumors outside the gastrointestinal tract are collectively referred to as extra GISTs, and stromal tumors in different regions often have different prognoses. A primary hepatic GIST is a rare tumor with an unknown origin, which may be related to interstitial Cajal-like cells. Although primary hepatic GIST has certain characteristics on imaging, it lacks specific symptoms and signs; thus, the final diagnosis depends on pathological and genetic evidence. This review summarizes all cases of primary hepatic GIST described in the literature and comprehensively analyzes the detailed clinical data of all patients. In terms of treatment, local resection alone or with adjuvant therapy was the prioritized choice to obtain better disease-free survival and longer survival time. For advanced unresectable cases, imatinib mesylate was applied as the first-line chemotherapy agent. Moreover, transcatheter arterial chemoembolization, radiofrequency ablation, and microwave ablation were shown to improve overall survival for selected patients. Liver transplantation was a final treatment option after resistance to chemotherapy developed.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/epidemiologia , Tumores do Estroma Gastrointestinal/terapia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Piperazinas/uso terapêutico , Prevalência , Pirimidinas
12.
Urology ; 143: 206-211, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32593627

RESUMO

OBJECTIVE: To evaluate and compare the surgical outcomes and complications of the modified circumcision using disposable circumcision suture device (device group) and the conventional dorsal slit circumcision (conventional group) in children. METHODS: A total of 284 patients were randomized to either device group or conventional group. All patients were preoperatively assessed and evaluated at 4 weeks after surgery. The perioperative data and postoperative outcomes were compared between the 2 groups. RESULTS: No statistical differences were observed in the average age and indications between the 2 groups preoperatively (P > .05). Compared with the conventional group, patients in the device group were shorter mean operative time, less blood loss, lower intraoperative and postoperative pain score, faster incision healing time and a higher satisfaction rate of penile cosmetic appearance (P < .01). Similarly, the incidences of complication were significantly lower in the device group than in the conventional group (4.3% vs 12.3%, P < .05). CONCLUSIONS: The modified circumcision using disposable circumcision suture device is a simple, safe, faster, and effective procedure and may become the attractive alternative to the conventional technique for the children, with a relatively lower complication rate and better cosmetic results. With the improvement of disposable circumcision suture device, the modified circumcision using disposable circumcision suture device has the potential to be widely used in the world.


Assuntos
Circuncisão Masculina/instrumentação , Edema/etiologia , Doenças do Pênis/etiologia , Adolescente , Perda Sanguínea Cirúrgica , Criança , Circuncisão Masculina/efeitos adversos , Circuncisão Masculina/métodos , Equipamentos Descartáveis , Humanos , Complicações Intraoperatórias/etiologia , Masculino , Duração da Cirurgia , Dor Pós-Operatória/etiologia , Satisfação do Paciente , Doenças do Pênis/cirurgia , Deiscência da Ferida Operatória/etiologia , Resultado do Tratamento , Cicatrização
15.
Cardiovasc Pathol ; 46: 107097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32086002

RESUMO

Benign smooth muscle tumors of the inferior vena cava (IVC) are unusual, but mostly consist of intravenous leiomyomatosis, which arises from the uterus. Primary leiomyoma of the IVC is extremely rare. Here, we report a primary leiomyoma of the IVC, misleadingly reported as a cystic neoplasm of the pancreas in images. Immunohistochemical analysis was positive for (estrogen receptor) ER and (progesterone receptor) PR, indicating gynecologic leiomyomas. The use of ER and PR immunostaining is recommended to help distinguish between somatic and gynecologic leiomyomas, whose criteria of malignancy differ.


Assuntos
Angiomioma/patologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Vasculares/patologia , Veia Cava Inferior/patologia , Angiomioma/química , Angiomioma/diagnóstico por imagem , Angiomioma/cirurgia , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/química , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico por imagem , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico por imagem , Valor Preditivo dos Testes , Resultado do Tratamento , Neoplasias Vasculares/química , Neoplasias Vasculares/diagnóstico por imagem , Neoplasias Vasculares/cirurgia , Veia Cava Inferior/química , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia
16.
Medicine (Baltimore) ; 98(48): e17815, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770197

RESUMO

To study the clinical significance of HINT2 expression in patients with HCC.We investigated HINT2 mRNA expression in tumors and adjacent non-tumor hepatic tissues from 106 HCC patients using quantitative real-time PCR. Appropriate statistical methods were then applied to assess the relationships between the HINT2 mRNA level and clinical parameters.HINT2 was significantly down-regulated in HCC (P < .0001). No significant correlation was found between HINT2 expression and clinicopathological factors in HCC patients. A Kaplan-Meier survival curve showed that HINT2 expression is related to recurrence-free survival (P < .05). Multivariate analyses revealed that tumor size and HINT2 expression are risk factors for HCC recurrence.HINT2 is down-regulated in HCC, and low HINT2 expression predicts earlier tumor recurrence. HINT2 expression may serve as a prognostic indicator of recurrence in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hepáticas/genética , Proteínas Mitocondriais/metabolismo , Recidiva Local de Neoplasia/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Regulação para Baixo/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco
17.
Exp Ther Med ; 18(4): 2608-2616, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31572509

RESUMO

Pancreatic cancer is a common malignancy that has a poor prognosis and limited therapeutic options. Enhancer of zeste homolog 2 (EZH2) serves a key role in the progression of different types of cancers. The effect of GSK343 (a competitive inhibitor of EZH2) on pancreatic cancer cells was assessed in the present study. Cell viability was evaluated using MTT and cell counting kit-8 assays in AsPC-1 and PANC-1 cells. Flow cytometry and an EdU assay were also performed to assess the effects of GSK343 on cell proliferation, apoptosis and the cell cycle. The induction of autophagy and associated molecular mechanisms were studied using fluorescence microscopy and western blot analysis. The results demonstrated that GSK343 inhibited cell viability in a dose- and time-dependent manner. Furthermore, GSK343 suppressed cell proliferation, promoted apoptosis and blocked cell cycle progression at the G1-phase. Furthermore, GSK343 induced autophagy in pancreatic cancer via the AKT/mTOR signaling pathway. In conclusion, GSK343 exhibited an anti-cancer effect on pancreatic cancer cells, downregulating the AKT/mTOR signaling pathway.

18.
Onco Targets Ther ; 12: 1691-1703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881024

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and limited therapeutic options. Ras-related associated with diabetes (RRAD) belongs to the subfamily of Ras-related GTPases and is associated with several types of cancer, including HCC, although the mechanisms involving RRAD in HCC remains unknown. PATIENTS AND METHODS: We aimed to elucidate the role of RRAD and whether it affects glucose metabolism in HCC by immunohistochemically examining tissue samples from HCC patients and assessing the effect of RRAD overexpression and knockdown on the glucose metabolism, proliferation, cell cycle, and apoptosis of HCC cell lines SK-Hep-1 and Huh7, as well as on tumor progression in vivo. RESULTS: We demonstrated that RRAD binds to actin gamma 1 (ACTG1). RRAD suppressed aerobic glycolysis in HCC by downregulating ACTG1. On the other hand, ACTG1 promoted HCC proliferation by regulating the cell cycle via downregulation of cyclins and cyclin-dependent kinases and inhibited apoptosis through the mitochondrial apoptosis pathway in vitro. In addition, RRAD retarded tumor growth by downregulating ACTG1 in vivo. ACTG1 was overexpressed in HCC tissues compared with adjacent normal tissues, whereas the expression of RRAD was low in tumor tissues. Low RRAD levels were significantly correlated with large tumor size and advanced tumor stage; high ACTG1 levels were significantly correlated with advanced tumor stage. Furthermore, Kaplan-Meier survival curves showed that HCC patients with high RRAD and low ACTG1 expression may have a better prognosis. CONCLUSION: We have shown that RRAD exhibits a tumor-suppressing role in HCC by downregulating glucose metabolism and ACTG1 expression, thus lowering cell proliferation, arresting the cell cycle, and increasing apoptosis. These findings indicate that ACTG1 may act as a downstream effector of RRAD and open a new avenue for potential HCC treatment.

19.
Medicine (Baltimore) ; 98(9): e14555, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817572

RESUMO

RATIONALE: Spindle cell hemangioma (SCH) is considered a benign vascular lesion. It typically develops as a solitary nodule or multiple masses located in the dermal or subcutaneous layers of the distal extremities. To the best of our knowledge, there are no prior reports of SCH in the spleen. PATIENT CONCERNS: A 41-year-old male was admitted to our hospital with recurrent headaches, nausea, and vomiting persisting for 5 days. Ultrasound, computed tomography, and magnetic resonance imaging revealed multiple space-occupying lesions in the spleen, and the biggest lesion was 4.8 cm × 5.4 cm in size. INTERVENTIONS: The patient underwent laparoscopic splenectomy. DIAGNOSIS: A diagnosis of spindle cell hemangioma of the spleen was made based on the histopathology. OUTCOMES: No evidence of local recurrence or distant metastases was observed over 4-year follow-up. LESSONS: Splenic SCH may exhibit relatively high proliferative activity and be comorbid with epithelioid hemangioendothelioma or angiosarcoma, raising the possibility of malignant potential. However, the patient remained alive and disease-free 4 years after the operation. The nature of SCH in deep soft tissues requires further study.


Assuntos
Hemangioma/patologia , Sarcoma/patologia , Neoplasias Esplênicas/patologia , Adulto , Humanos , Masculino , Baço/patologia
20.
World J Clin Cases ; 7(2): 236-241, 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30705901

RESUMO

BACKGROUND: Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive epithelial tumor that has both epithelial and mesenchymal features. It is characterized by sarcomatous elements with evidence of epithelial differentiation. And the term "sarcomatoid carcinoma" is often confused with "carcinosarcoma". CASE SUMMARY: We present a case of SCP with lymph node metastasis in a 59-year-old male patient. He had experienced darkening of the urine, scleral icterus, and fatigue for 4 weeks. Computed tomography and magnetic resonance imaging revealed a mass in the pancreatic head, and laboratory tests revealed elevated serum bilirubin levels. The patient underwent pancreaticoduodenectomy after biliary decompression. Histologically, spindle cells with marked nuclear atypia and brisk mitotic activity arranged in a storiform or fascicular pattern were present in the bulk of the tumor. Immunohistochemical analysis found that the spindle cells exhibited strong diffuse positivity for epithelial markers, indicative of epithelial differentiation. Accordingly, the pathologic diagnosis of the pancreatic neoplasm was SCP. CONCLUSION: Although sarcomatoid carcinomas and carcinosarcomas have different pathologic features, both have epithelial origin.

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