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1.
Cancer Gene Ther ; 31(5): 687-697, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38347129

RESUMO

SMARCA4-deficient undifferentiated thoracic tumor is extremely invasive. This tumor with poor prognosis is easily confused with SMARCA4-deficent non-small cell lung cancer or sarcoma. Standard and efficient treatment has not been established. In this review, we summarized the etiology, pathogenesis and diagnosis, reviewed current and proposed innovative strategies for treatment and improving prognosis. Immunotherapy, targeting tumor microenvironment and epigenetic regulator have improved the prognosis of cancer patients. We summarized clinicopathological features and immunotherapy strategies and analyzed the progression-free survival (PFS) and overall survival (OS) of patients with SMARCA4-UT who received immune checkpoint inhibitors (ICIs). In addition, we proposed the feasibility of epigenetic regulation in the treatment of SMARCA4-UT. To our knowledge, this is the first review that aims to explore innovative strategies for targeting tumor microenvironment and epigenetic regulation and identify potential benefit population for immunotherapy to improve the prognosis.


Assuntos
DNA Helicases , Epigênese Genética , Imunoterapia , Neoplasias Torácicas , Fatores de Transcrição , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Imunoterapia/métodos , DNA Helicases/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias Torácicas/genética , Neoplasias Torácicas/terapia , Neoplasias Torácicas/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico
2.
Sensors (Basel) ; 23(12)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37420886

RESUMO

Under the trend of vehicle intelligentization, many electrical control functions and control methods have been proposed to improve vehicle comfort and safety, among which the Adaptive Cruise Control (ACC) system is a typical example. However, the tracking performance, comfort and control robustness of the ACC system need more attention under uncertain environments and changing motion states. Therefore, this paper proposes a hierarchical control strategy, including a dynamic normal wheel load observer, a Fuzzy Model Predictive Controller and an integral-separate PID executive layer controller. Firstly, a deep learning-based dynamic normal wheel load observer is added to the perception layer of the conventional ACC system and the observer output is used as a prerequisite for brake torque allocation. Secondly, a Fuzzy Model Predictive Control (fuzzy-MPC) method is adopted in the ACC system controller design, which establishes performance indicators, including tracking performance and comfort, as objective functions, dynamically adjusts their weights and determines constraint conditions based on safety indicators to adapt to continuously changing driving scenarios. Finally, the executive controller adopts the integral-separate PID method to follow the vehicle's longitudinal motion commands, thus improving the system's response speed and execution accuracy. A rule-based ABS control method was also developed to further improve the driving safety of vehicles under different road conditions. The proposed strategy has been simulated and validated in different typical driving scenarios and the results show that the proposed method provides better tracking accuracy and stability than traditional techniques.


Assuntos
Movimento (Física) , Tempo de Reação
3.
Langenbecks Arch Surg ; 408(1): 208, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37222797

RESUMO

PURPOSE: Conformal sphincter preservation operation (CSPO) procedure is a sphincter preservation procedure for preserving the anal canal function for very low rectal cancers. This study investigated the functional and oncological outcome of conformal sphincter preservation operation by comparing with low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: This is a retrospective comparative study. Patients who received conformal sphincter preservation operation (n = 52), low anterior resection (n = 54), or abdominoperineal resection (n = 69) were included between 2011 and 2016 in a tertiary referral hospital. Propensity score matching was applied to adjust the baseline characteristics which may influence the choice of the surgical procedure. RESULTS: Twenty-one pairs of conformal sphincter preservation operation vs. low anterior resection and 29 pairs of conformal sphincter preservation operation vs. abdominoperineal resection were selected. The first group had a higher tumor location than the second group. Compared with the low anterior resection group, the conformal sphincter preservation operation group had shorter distal resection margins; however, no significant differences were identified in daily stool frequency, Wexner incontinence score, local recurrence, distant metastasis, overall survival, and disease-free survival between both groups. Compared with the abdominoperineal resection group, the conformal sphincter preservation operation group had shorter operative time and shorter postoperative hospital stay. No significant differences were identified in local recurrence, distant metastasis, overall survival, and disease-free survival. CONCLUSION: Conformal sphincter preservation operation is oncologically safe compared to APR and LAR, and has similar functional findings to LAR. Studies comparing CSPO with intersphincteric resection should be performed.


Assuntos
Neoplasias , Protectomia , Humanos , Estudos de Coortes , Pontuação de Propensão , Estudos Retrospectivos , Canal Anal/cirurgia
4.
Eur Radiol ; 33(2): 1353-1363, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35997838

RESUMO

OBJECTIVE: To investigate the feasibility of b-value threshold (bThreshold) map in preoperative evaluation of tumor budding (TB) in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC were enrolled and underwent diffusion-weighted imaging (DWI). Contrast-to-noise ratio (CNR) between the lesions and normal tissues was assessed using DWI and bThreshold maps. TB was counted and scored using hematoxylin and eosin staining. Reproducibility for the apparent diffusion coefficient (ADC), bThreshold values, and region-of-interest (ROI) sizes were compared. Differences in ADC and bThreshold values with low-intermediate and high TB grades and the correlations between mean ADC and bThreshold values with TB categories were analyzed. Diagnostic performance of ADC and bThreshold values was assessed using area under the curve (AUC) and decision curve analysis. RESULTS: Fifty-one patients were evaluated. The CNR on bThreshold maps was significantly higher than that on DW images (9.807 ± 4.811 vs 7.779 ± 3.508, p = 0.005). Reproducibility was excellent for the ADC (ICC 0.933; CV 8.807%), bThreshold values (ICC 0.958; CV 7.399%), and ROI sizes (ICC 0.934; CV 8.425%). Significant negative correlations were observed between mean ADC values and TB grades and positive correlations were observed between mean bThreshold values and TB grades (p < 0.05). bThreshold maps showed better diagnostic performance than ADC maps (AUC, 0.914 vs 0.726; p = 0.048). CONCLUSIONS: In LARC patients, bThreshold values could distinguish different TB grades better than ADC values, and bThreshold maps may be a preoperative, non-invasive approach to evaluate TB grades. KEY POINTS: • Compared with diffusion-weighted images, bThreshold maps improved visualization and detection of rectal tumors. • Agreement and diagnostic performance of bThreshold values are superior to apparent diffusion coefficient in assessing tumor budding grades in patients with locally advanced rectal cancer. • bThreshold maps could be used to evaluate tumor budding grades non-invasively before operation.


Assuntos
Adenocarcinoma , Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Reprodutibilidade dos Testes , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Reto/patologia , Adenocarcinoma/diagnóstico por imagem
5.
Front Immunol ; 13: 1031171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311804

RESUMO

Background: Immunotherapy (Programmed cell death 1 blockade) has entered the ranks of advanced esophageal cancer first-line treatment; however, little is known about the efficacy of PD-1 inhibitor as neoadjuvant therapy in resectable esophageal squamous cell carcinoma (ESCC). We aim to evaluate the activity and safety of the neoadjuvant sintilimab combined with chemotherapy in the treatment of resectable thoracic ESCC. Methods: The enrolled patients with resectable (clinical stage II to IVA) ESCC received neoadjuvant sintilimab injection (200 mg/time, day 1), paclitaxel liposomes (135 mg/m2, day 1), and carboplatin (area under curve of 5 mg/mL/min, day 1) every 21 days for 2 cycles, and esophagectomy was performed within 3-6 weeks after the 2 cycles of treatment. The primary endpoint of the study was the pathological complete response (PCR) rate. Results: From July 2019 to March 2021, a total of 47 patients were enrolled, of which 33 patients (70.2%) had clinical stage III disease. All patients completed the full two-cycle treatment and forty-five patients received radical surgery, including 44 (97.8%) R0 resections. Ten (22.2%) of 45 patients had a PCR, and the major pathological response (MPR) rate was 44.4% (20/45). The grade 3-4 treatment-related adverse events (TRAEs) were mainly neutropenia (6 of 47,12.8%) and leucopenia (8 of 47,17.0%). One (2.1%) patient occurred postoperative immune-associated encephalitis. No delays in surgery were observed. Conclusions: sintilimab combined with paclitaxel liposome and carboplatin, as demonstrated in this phase II trial to exhibit a relatively high PCR rate and acceptable safety, warrants additional investigation in resectable ESCC. Trial Registration: http://www.chictr.org.cn/, ChiCTR1900026593.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Carboplatina/efeitos adversos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel
6.
World J Surg Oncol ; 20(1): 296, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104818

RESUMO

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Formaldeído , Humanos , Margens de Excisão , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia
7.
Materials (Basel) ; 15(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36079458

RESUMO

The iron and steel industry is a major CO2 emitter and an important subject for the implementation of carbon emission reduction goals and tasks. Due to the complex ore composition and low iron grade, vanadium-bearing titanomagnetite smelting in a blast furnace consumes more coke and emits more carbon than in an ordinary blast furnace. Injecting hydrogen-rich gas into blast furnace can not only partially replace coke, but also reduce the carbon emission. Based on the whole furnace and zonal energy and mass balance of blast furnace, the operation window of the blast furnace smelting vanadium-bearing titanomagnetite is established in this study on the premise that the thermal state of the blast furnace is basically unchanged (raceway adiabatic flame temperature and top gas temperature). The effects of different injection amounts of hydrogen-rich gases (shale gas, coke oven gas, and hydrogen) on raceway adiabatic flame temperature and top gas temperature, and the influence of blast temperature and preheating temperature of hydrogen-rich gases on operation window are calculated and analyzed. This study provides a certain theoretical reference for the follow-up practice of hydrogen-rich smelting of vanadium-bearing titanomagnetite in blast furnace.

8.
J Cancer Res Clin Oncol ; 147(4): 1065-1075, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33389076

RESUMO

PURPOSE: Imatinib, a small-molecule tyrosine kinase inhibitor, has shown good clinical activity by inhibiting adenosine triphosphate (ATP) binding to the receptor. Unfortunately, majority of patients eventually develop drug resistance, which limits the long-term benefits of the tyrosine kinase inhibitors and poses a significant challenge in the clinical management of GIST. The aim of our study was to explore the feasibility of blocking KIT dimerisation upstream of the phosphorylation in imatinib-resistant GIST. METHOD: KITMAb was prepared using hybridoma technique. The biological function of KITMAb was examined in KIT-dimer-expressing cells constructed by transfecting with liposomes using enzyme linked immunosorbent assay (ELISA), immunohistochemistry, western blot, MTT, Annexin V/FITC, and flow cytometry assay, respectively. RESULTS: KIT-dimer was expressed in 293 cells transfected with c-kit mutated-type pcDNA3.1. Treatment of KIT-dimer-expressing cells with the KITMAb significantly decreased the expression of both KIT-dimer and other phosphorylated proteins of KIT downstream signalling pathway. Furthermore, KITMAb slowed down cell growth and reduced the proportion of cells in the proliferative phase (S + G2-M). Finally, we also found that KITMAb treatment accelerated cell apoptosis. These results indicate that KITMAb strongly inhibits KIT receptor dimerisation-mediated signalling pathway and cell growth responses in vitro. CONCLUSIONS: We demonstrate c-kit mutation-driven KIT auto-dimerisation prior to tyrosine kinase phosphorylation as same as the procedure in ligand-dependent signalling pathway and describe a monoclonal antibody, KITMAb, with strong affinity to the dimerisation domain of KIT that blocks the important step in both the KIT signalling pathways. Further, the results suggest that treatment with KITMAb may be potentially therapeutic in imatinib-resistant GIST.


Assuntos
Anticorpos Monoclonais/farmacologia , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Mutação , Neoplasias/patologia , Multimerização Proteica , Proteínas Proto-Oncogênicas c-kit/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Ciclo Celular , Proliferação de Células , Humanos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-kit/química , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/imunologia , Células Tumorais Cultivadas
10.
Cancer Cell ; 38(5): 734-747.e9, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888432

RESUMO

We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Genômica/métodos , Metástase Neoplásica/tratamento farmacológico , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteômica/métodos , Animais , Antineoplásicos/farmacologia , China , Estudos de Coortes , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Terapia de Alvo Molecular , Metástase Neoplásica/genética , Fosforilação , Medicina de Precisão , Prognóstico , Proteínas Quinases/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Gastroenterol Res Pract ; 2020: 2052561, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32256564

RESUMO

BACKGROUND: The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. METHOD: Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. RESULTS: X-tile plots identified 3 (P < 0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P < 0.001, P = 0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P < 0.001). CONCLUSION: More TD count (TD count ≥ 4) was significantly associated with poor disease-specific survival in CRC patients.

12.
Transl Cancer Res ; 9(10): 6528-6533, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35117261

RESUMO

Gastrointestinal clear cell sarcomas (GICCSs) are malignant mesenchymal tumour that occur in the wall of gastrointestinal tract, mostly in the ileum and rarely in the rectum. These tumours are highly invasive, and often have metastasized via the lymphatic system or bloodstream by the time of diagnosis. In this case, the patient was admitted for gastric fundus mass, who was subsequently found and confirmed by biopsy as clear cell sarcoma of rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple metastatic lesions in lymph node, lung, liver and bone. Furthermore, energy spectrum CT was used to confirm that the nature of gastric fundus mass and rectal lesion were consistent. So, this case may be multiple clear cell sarcomas in the rectum and stomach or clear cell sarcoma in the rectum with gastric fundus metastasis. Unfortunately, after several days of immunotherapy, the patient died due to abnormal liver function. At present, GICCS mainly relies on surgical resection, and the effect of radiotherapy and chemotherapy is not good. Therefore, how to find lesions as earlier as possible and make accurate diagnosis is particularly important. CT and MRI are essential examinations in the diagnosis of tumors. Whether they are helpful for the diagnosis of GICCS is the focus of our attention.

13.
Cancer Imaging ; 19(1): 83, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801587

RESUMO

BACKGROUND: To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. METHODS: A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. RESULTS: There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques. CONCLUSIONS: HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Junção Esofagogástrica , Imageamento por Ressonância Magnética/métodos , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologia
14.
Cancer Biol Ther ; 20(5): 642-652, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30621501

RESUMO

BACKGROUND: Hypoxia may affect the therapeutic efficacy of transcatheter arterial embolization (TAE), which is widely used in nonsurgical hepatocellular carcinoma (HCC). Liposomal curcumin can exert anticancer effect. Our purpose is to explore the antitumor effect of liposomal curcumin on the HCC after TAE. METHODS: The HepG2 cells were cultured under hypoxic condition (1% O2) and then treated with curcumin liposome. Cell viability, apoptosis and cell cycle were respectively measured by CCK-8 and a flow cytometry. The VX2 rabbits were randomly distributed into three groups: control group with saline embolization, TAE group with lipiodol embolization and curcumin liposome group with curcumin liposome and lipiodol embolization. MRI and CT perfusion scanning were performed after embolization. The hepatocyte apoptosis was measured by the terminal deoxyribonucleotidyl transferse-mediated dUTP nick-end labelling (TUNEL). The vascular endothelial growth factor (VEGF) and microvessel density (MVD) were measured by immunohistochemical. RT-PCR and Western blot were performed to examine mRNA and protein levels. RESULTS: By regulating the apoptosis-related molecules, curcumin liposome obviously inhibited the cell viability and promoted the apoptosis in G1 phase. Curcumin liposome reduced the tumor size and alleviated neoplasia in VX2 rabbits. Curcumin liposome decreased the expressions of MVD and VEGF and increased the apoptosis of liver tissues. The levels of hypoxia-inducible factor-1α (HIF-1α) and survivin were suppressed by curcumin liposome both in hypoxic cells and liver tissues in the VX2 rabbits. CONCLUSION: Curcumin liposome exerted antitumor effect by regulating the proliferation- and apoptosis-related molecules. Curcumin liposome suppressed the HIF-1α and survivin levels and inhibited the angiogenesis in VX2 rabbits after TAE.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Curcumina/administração & dosagem , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células , Terapia Combinada/métodos , Modelos Animais de Doenças , Células Hep G2 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lipossomos , Neoplasias Hepáticas/patologia , Coelhos , Survivina/antagonistas & inibidores , Survivina/metabolismo
15.
Gastric Cancer ; 22(1): 91-103, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29948390

RESUMO

BACKGROUND: FoxM1 plays important regulatory roles in a variety of diseases. However, the functional role of FoxM1 and mechanisms responsible for its expression in gastrointestinal stromal tumor (GIST) is not thoroughly understood. METHODS: FoxM1 protein expression and biological function were examined in human GIST tissues and cells using immunohistochemistry, quantitative real-time PCR, western blot, CCK-8, wound-healing- and Matrigel invasion assays, respectively. The role of hypoxia-inducible factor (HIF) signaling in FoxM1 expression was investigated using chromatin immunoprecipitation and luciferase reporter and in vivo tumor growth assays. RESULTS: FoxM1 was highly expressed in highly proliferative and migratory/invasive GIST specimens. Upregulation of FoxM1 was positively correlated with the expression of HIF-1α and HIF-2α in GIST specimens, and hypoxia-induced FoxM1 expression in GIST cells. Functionally, ectopic expression of FoxM1 significantly promoted GIST cell proliferation, cell cycle progression, migration and invasion, whereas the knockdown of endogenous FoxM1 of hypoxic GIST cells had the opposite effects. Molecularly, FoxM1 was transcriptionally regulated by HIF-2α under normoxia, whereas it was upregulated by both HIF-1α and HIF-2α under hypoxia. The xenograft tumor data further confirmed the regulated effect of HIF-1α and HIF-2α on FoxM1, and demonstrated that the simultaneous downregulation of both HIF-1α and HIF-2α inhibited GIST tumor growth. CONCLUSIONS: Our data demonstrated the critical role of FoxM1 in promoting GIST progression and uncovered a novel HIF-1α/HIF-2α-FoxM1 axis. These findings identify FoxM1 as a possible new molecular target for designing novel therapeutic treatments to control GIST progression.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteína Forkhead Box M1/biossíntese , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade
16.
J Hazard Mater ; 357: 128-137, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29870897

RESUMO

A cleaner process is tremendously required to deal with the vanadium tailings, which may cause serious environmental problem due to the high content of water soluble hazardous elements such as V and Cr. This problem can be possibly solved by proposed high temperature reduction-magnetic separation process, in which, V, Cr and Fe can be recycled as ferroalloy. The thermodynamic calculation results reveal that a higher temperature (>1127.8 °C) promotes the reduction of Fe, V and Cr, and improves the recovery rates of V and Cr in liquid iron. The reduction behavior of vanadium tailings was investigated using XRD, TG/DSC, SEM, EDS and ICP-OES techniques. The EDS results show that a small portion of V was remained in the slag phase when roasted at 1300 °C, while nearly all of V and Cr can concentrate in ferroalloy at 1400 °C. Approximatly 90% of V and 95% of Cr recovery in magnetic fraction can be obtained for the magnetic separation step. A small portion of V and Cr is remained in the non-magnetic final tailings, however, the hazardous potential assessments results indicate that such kind of tailings can safely use as secondary materials or stockpiled as an end-waste.

17.
Hum Pathol ; 76: 76-84, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29486292

RESUMO

Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem cell precursors, and expresses stemness-related markers, such as CD117, CD34, DOG1 and nestin. To further characterize phenotypic features of GISTs, we examined expression profiles of a panel of stemness genes in GISTs, by analyzing existing gene expression profiling datasets. Our results showed that mRNA levels of B-lymphoma moloney murine leukaemia virus insertion region-1 (BMI1), kruppel-like factor 4 (KLF4), sal-like protein 4 (SALL4) and telomerase reverse transcriptase (TERT) were significantly unregulated in GISTs. Subsequently, protein expression of BMI1 and TERT was identified in GIST specimens by immunohistochemistry. Especially, we found that high expression of nuclear BMI1 was associated with large tumor size (P = .0239), high mitotic count (P < .01), high Ki-67 index (P = .0357), advanced National Institute of Health (NIH) criteria (P = .0025) and advanced World Health Organization (WHO) classification (P < .01) in GISTs. Functional and pathway enrichment analysis showed that most of BMI1's coexpressed genes were involved in tumor growth-related process, such as regulation of cell cycle and proliferation. Furthermore, we confirmed RAS oncogene family (RAB18) and limb development membrane protein 1 (LMBR1) genes as novel targets for BMI1 in GIST cells. These results provide valuable information for the expression profiles of stemness genes in GISTs, and identified nuclear BMI1 as an important marker of GIST cell proliferation and progression.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Células-Tronco Neoplásicas/metabolismo , Transcriptoma , Biomarcadores Tumorais/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Proliferação de Células/genética , Bases de Dados Genéticas , Progressão da Doença , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , RNA Mensageiro/genética
18.
J Hazard Mater ; 336: 1-7, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28463734

RESUMO

A multistage utilization process was developed to fully recover valuable metals from vanadium-bearing converter slag and reduce the content of hazardous elements, such as vanadium and chromium, in the tailings. A mechanical activation-calcification roasting-acid leaching process was firstly employed to recover vanadium. This process generated two products, viz. a V-bearing solution accounting for ∼95% V recovery and vanadium tailings with Fe and Ti contents of 31.85% and 8.94%, respectively. Then, based on theoretical calculations and physical measurements, a coal-based direct reduction-magnetic separation process and a hydrochloric acid leaching process were employed for the stepwise recovery of iron and titanium, respectively, from the vanadium tailings. Iron was recovered in the form of high chromium-vanadium iron with 81.53% Fe, 1.31% Cr, and 2.04% V, and titanium was recovered as titanium dioxide pigment with 85-90% yield. Such a comprehensive and clean utilization of vanadium-bearing converter slag has great potential for practical application.

19.
Medicine (Baltimore) ; 96(9): e6018, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28248859

RESUMO

RATIONALE: Primary angiitis of the central nervous system (PACNS) is an inflammatory disease involving cerebrovascular and parenchymal, and solitary tumor-like mass lesion of PACNS (TLML-PACNS) is frequently misdiagnosed as neoplastic or other inflammatory diseases. However, seizure syndrome as a first manifestation of TLML-PACNS has rarely reported before. PATIENT CONCERNS: Here, we report 2 cases of seizure syndrome, which was the first sign that presented prior to the diagnosis of TLML-PACNS by brain biopsy. DIAGNOSES: A mass lesion in the white and gray matters was detected by magnetic resonance imaging. The pathology for leptomeningeal lesion biopsy observed a transmural inflammation of the artery, with T lymphocyte infiltration. Patients were diagnosed with PACNS and epileptic seizure by biopsy and electroencephalogram. INTERVENTIONS: Patients were treated with glucocorticoid pulse therapy for 3 days, and subsequently oral prednisone was continued, in combination with immunosuppressant. OUTCOMES: Luckily, both two patients were improved after treatment, and only mild cognitive impairment remained without adverse event. LESSONS: Patient with mass lesion in CNS, which is similar to tumor, presented with seizure, headache, or cerebrovascular events without any other risk factors for stroke or tumor, should be considered the feasible with the disease of TLML-PACNS.


Assuntos
Convulsões/etiologia , Vasculite do Sistema Nervoso Central/diagnóstico , Adulto , Imagem de Difusão por Ressonância Magnética , Eletroencefalografia , Humanos , Angiografia por Ressonância Magnética , Masculino , Neuroimagem , Síndrome , Tomografia Computadorizada por Raios X , Vasculite do Sistema Nervoso Central/complicações , Adulto Jovem
20.
Int J Clin Exp Pathol ; 10(9): 9273-9283, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966799

RESUMO

OBJECTIVE: To investigate the expression of long-chain non-coding RNAs DAPK1 and miR-182 in pancreatic cancer tissues and the role of DAPK1 and miR-182 in pancreatic cancer cell invasion and migration and its mechanism. METHODS: The expression of DAPK1 and miR-182 in different pancreatic cancer and adjacent tissues and different pancreatic cancer cells were detected by qPCR. Transwell invasion assay was used to detect the invasion ability of pancreatic cancer cells after DAPK1 expression. The changes of the migration ability of pancreatic cancer cells after DAPK1 expression were detected by scratch test. Double luciferase reporter gene was used to detect the interaction between DAPK1 and miR-182. Transwell invasion assay showed that miR-182 overexpression of DAPK1 could restore the invasive ability of pancreatic cancer cells. Western blot was used to detect the expression of ROCK-1/RhoA pathway protein after overexpression of miR-182 in DAPK1 cells. Phalloidin was used to label the cytoskeleton. The effect of miR-182 overexpression of DAPK1 on tumor size and volume of pancreatic cancer was detected by subcutaneous tumor formation in nude mice. RESULTS: The expression of DAPK1 was significantly decreased in pancreatic cancer tissues compared with adjacent tissues, and the expression of DAPK1 decreased gradually and the expression of miR-182 was opposite with the progression of tumor. DAPK1 was associated with pathological stage of pancreatic cancer and lymph node metastasis, while miR-182 was positively correlated. The expression level of DAPK1 in pancreatic cancer cell HS766T was the lowest. Overexpression of DAPK1 could inhibit the invasion and migration of pancreatic cancer cells. DAPK1 could bind specifically to 3'UTR of miR-182. Overexpression of miR-182 could restore the invasion and migration of pancreatic cancer cells after overexpression of DAPK1. The expression of ROCK-1/RhoA pathway protein was down-regulated by miR-182 after expression of DAPK1, and the expression of ROCK-1/RhoA pathway protein was restored. The expression of F-actin in LV5-DAPK1 group was significantly decreased, the formation of cell membrane wrinkles was significantly reduced, and the formation of pseudopodia was significantly reduced compared with LV5-DAPK1 + miR-182-mimic group. The tumor volume and weight of tumor-bearing mice in LV5-DAPK1 + miR-182-mimic group were significantly increased compared with LV5-DAPK1 group. CONCLUSION: DAPK1 plays an important role in the development and progression of pancreatic cancer. DAPK1 can regulate the invasion and migration of pancreatic cancer cells through the regulation of miR-82 through ROCK-1/RhoA signaling pathway.

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