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1.
J Natl Cancer Inst ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637942

RESUMO

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

2.
Anticancer Res ; 44(3): 1121-1130, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423629

RESUMO

BACKGROUND/AIM: Chronic lymphocytic leukemia is a slowly-progressing disease in which symptoms often do not manifest until years after disease onset. In advanced stages, infection and bleeding are common. Past studies have shown that the interaction between CDK4/6 inhibitors and chemotherapy drugs can enhance the anti-tumor efficacy of drugs and limit toxicity. Therefore, in this study, the treatment effects of combining the CDK4/6 inhibitor LEE011 with chemotherapy drugs bendamustine or hydroxyurea were investigated in vitro. MATERIALS AND METHODS: The mouse lymphocytic leukemia cell line L1210 was treated with LEE011 combined with hydroxyurea or bendamustine. Western blot and flow cytometry were performed to elucidate the mechanisms behind tumor suppression. RESULTS: LEE011 combined with hydroxyurea or bendamustine significantly inhibited proliferation of L1210 cell lines in a concentration- and time-dependent manner as well as increased the arrest of cells in G1 and S phases. The combination of LEE011 with hydroxyurea also reduced the phosphorylation of Rb while increased the expression of total Rb protein. Furthermore, reduced expression of GPX4, which is a key protein in ferroptosis, indicates that the tumor suppression effects of this drug combination could involve ferroptosis. CONCLUSION: CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.


Assuntos
Aminopiridinas , Hidroxiureia , Neoplasias , Purinas , Animais , Camundongos , Proliferação de Células , Hidroxiureia/farmacologia , Cloridrato de Bendamustina , Proteínas Inibidoras de Quinase Dependente de Ciclina , Quinase 4 Dependente de Ciclina , Linhagem Celular Tumoral
3.
BMC Med ; 21(1): 464, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012705

RESUMO

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/genética , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Prognóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Imageamento por Ressonância Magnética/métodos
4.
Int J Colorectal Dis ; 38(1): 243, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37779168

RESUMO

PURPOSE: The present study aims to determine the rectoanal colonization rate and risk factors for the colonization of present multidrug-resistant bacteria (MDRBs). In addition, the relationship between MDRB colonization and surgical site infection (SSI) following hemorrhoidectomy was explored. METHODS: A cross-sectional study was conducted in the Department of Colorectal Surgery of two hospitals. Patients with hemorrhoid disease, who underwent hemorrhoidectomy, were included. The pre-surgical screening of multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization was performed using rectal swabs on the day of admission. Then, the MDRB colonization rate was determined through the rectal swab. Logistic regression models were established to determine the risk factors for MDRB colonization and SSI after hemorrhoidectomy. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 432 patients met the inclusion criteria, and the MDRB colonization prevalence was 21.06% (91/432). The independent risk factors for MDRB colonization were as follows: patients who received ≥ 2 categories of antibiotic treatment within 3 months (odds ratio (OR): 3.714, 95% confidence interval (CI): 1.436-9.605, p = 0.007), patients with inflammatory bowel disease (IBD; OR: 6.746, 95% CI: 2.361-19.608, p < 0.001), and patients with high serum uric acid (OR: 1.006, 95% CI: 1.001-1.010, p = 0.017). Furthermore, 41.57% (37/89) of MDRB carriers and 1.81% (6/332) of non-carriers developed SSIs, with a total incidence of 10.21% (43/421). Based on the multivariable model, the rectoanal colonization of MDRBs (OR: 32.087, 95% CI: 12.052-85.424, p < 0.001) and hemoglobin < 100 g/L (OR: 4.130, 95% CI: 1.556-10.960, p = 0.004) were independently associated with SSI after hemorrhoidectomy. CONCLUSION: The rectoanal colonization rate of MDRBs in hemorrhoid patients is high, and this was identified as an independent risk factor for SSI after hemorrhoidectomy.


Assuntos
Infecções Bacterianas , Hemorroidectomia , Hemorroidas , Humanos , Infecções Bacterianas/microbiologia , Estudos Transversais , Hemorroidectomia/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Hemorroidas/cirurgia , Hemorroidas/tratamento farmacológico , Ácido Úrico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Fatores de Risco , Bactérias Gram-Negativas
5.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555391

RESUMO

Globally, there are over half a million new patients with head and neck squamous cell carcinomas (HNSCC) every year. The current therapeutic approaches to HNSCC are surgery and adjuvant radiotherapy. These approaches carry a high incidence of metastasis or recurrence from HNSCC cells' radioresistance. Recent studies have revealed that a combination with radiosensitizers can be used to improve the radioresistance in HNSCC; however, few agents are approved as radiosensitizers. The constitutive activation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a vitally oncogenic type of signaling that promotes tumorigenesis, metastasis, and radiotherapy resistance in HNSCC. Pharmacological targeting of PI3K/AKT/mTOR signaling pathway is considered a promising strategy of radiosensitization in HNSCC. In this review, we summarize the oncogenic significance of PI3K/AKT/mTOR signaling in HNSCC with radiotherapy resistance and highlight the therapeutic potential of small molecule inhibitors against PI3K/AKT/mTOR signaling for the radiosensitization in HNSCC treatment. It provides a mechanistic framework for the development of new drugs for radiosensitization in HNSCC radiotherapy via targeting PI3K/AKT/mTOR signaling pathway.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas Proto-Oncogênicas c-akt , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral
6.
Sensors (Basel) ; 22(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36433443

RESUMO

Accurate distance estimation is a requirement for advanced driver assistance systems (ADAS) to provide drivers with safety-related functions such as adaptive cruise control and collision avoidance. Radars and lidars can be used for providing distance information; however, they are either expensive or provide poor object information compared to image sensors. In this study, we propose a lightweight convolutional deep learning model that can extract object-specific distance information from monocular images. We explore a variety of training and five structural settings of the model and conduct various tests on the KITTI dataset for evaluating seven different road agents, namely, person, bicycle, car, motorcycle, bus, train, and truck. Additionally, in all experiments, a comparison with the Monodepth2 model is carried out. Experimental results show that the proposed model outperforms Monodepth2 by 15% in terms of the average weighted mean absolute error (MAE).


Assuntos
Condução de Veículo , Humanos , Veículos Automotores , Motocicletas
7.
Front Psychiatry ; 13: 978660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325533

RESUMO

Background: To understand the occurrence of post-traumatic stress disorder (PTSD) and the current status of sleep quality among community-dwelling elderly adults in Hunan Province of China, to explore the correlation between the two, and to analyze the trend of sleep disorders in PTSD elderly adults. Methods: A simple random sample containing 1,173 community-dwelling elderly adults in Hunan Province was established between March and May 2022, and an on-site face-to-face survey was administered using the PTSD Checklist-Civilian Version (PCL-C) with good reliability and validity, the Pittsburgh Sleep Quality Index (PSQI) scale, and a self-designed general condition questionnaire. Results: The incidence of PTSD in the 1,173 participants was 14.3% (168/1,173). The total incidence of sleep disorders was 40.9% (480/1,173); more specifically, the incidence of sleep disorders in participants with no PTSD symptom, in participants with mild-to-moderate PTSD symptoms, and in participants with severe PTSD symptoms was 36.3, 69.8, and 66.7%, respectively. The Spearman's rank correlation analysis showed that the total PTSD score and the scores of each dimension (i.e., re-experiencing symptom cluster, avoidance symptom cluster and hypervigilance symptom cluster) were positively correlated with the total PSQI score and its dimension scores (i.e., sleep quality, time to fall asleep, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication, and daytime function) (P < 0.05). The correlation coefficients ranged from 0.013 to 0.495. For all PSQI dimensions, the differences across participants with different degrees of PTSD were statistically significant (P < 0.05). Conclusions: The overall status of PTSD and sleep quality in community-dwelling elderly adults in Hunan Province was not optimistic. The elderly with PTSD were more prone to sleep disorders, and the more severe the symptoms of PTSD, the poorer the sleep quality was. However, differences were observed in the scores of each dimension of sleep across participants with different degrees of PTSD. Regardless of the degree of PTSD symptoms, the sleep quality of the elderly is severely affected, and the occurrence rate is not unlimited.

8.
ACS Omega ; 6(48): 33192-33199, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34901670

RESUMO

The bifunctional ligands of isonicotinic acid (Py-4-COOH) and 4-pyrid-4-ylbenzoic acid (Pybz-4-COOH) instead of polypyridines were therefore reacted with (Re(CO)4)3(C3N3S3) (C3N3S3 = cyanurate trianion), resulting in the formation of two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COOH)3] (1) and [(Re(CO)3)3(C3N3S3)(Pybz-4-COOH)3] (2), respectively. In the meantime, both complexes 1 and 2 are connected by three bifurcated hydrogen bonds between their carboxylic acid moieties Py-4-COOH and Pybz-4-COOH to form the supramolecular trigonal-prismatic and -antiprismatic structures, respectively. It is noted that complex 1 can further react with copper(II) nitrate upon deprotonation to give nonanuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)9 (3), where two trinuclear [(Re(CO)3)3(C3N3S3)(Py-4-COO)3] moieties are connected by three penta-coordinate copper(II) ions, each coordinating to two carboxylates and three water molecules, to form the trigonal-prismatic structure. Surprisingly, addition of pyrazine (pz) in the synthetic process of complex 3 resulted in serendipitous isolation of a rare example of octadecanuclear {[(Re(CO)3)3(C3N3S3)(Py-4-COO)3]2Cu3(H2O)6(pz)2}2 (4), which can be regarded as a dimer of complex 3, connected by two bridging pz ligands. Interestingly, both complexes 3 and 4 are heteronuclear molecular Re(I)-Cu(II) boxes, constructed by a complex-as-a-ligand strategy. Furthermore, complexes 1 and 2 can exhibit respective low-energy luminescence at ca. 561 and 534 nm at room temperature upon photoexcitation, and complex 3 is found to display antiferromagnetic coupling of -127.68 and -134.70 cm-1, possibly due to multiple hydrogen bonds inducing significant Cu(II)···Cu(II) coupling.

9.
Front Pharmacol ; 12: 720368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690763

RESUMO

The Na+/K+-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na+/K+ exchange, metabolism, signal transduction, etc. In vivo, we found that Panax notoginseng saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined in vitro. Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na+/K+-ATPase inhibitor (digitonin) and sorafenib in vitro. We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells via downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.

10.
Biology (Basel) ; 10(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671283

RESUMO

Djulis (Chenopodium formosanum Koidz.) is a species of cereal grain native to Taiwan. It is rich in dietary fibre and antioxidants and therefore reputed to relieve constipation, suppress inflammation, and lower blood glucose. The aim of this study was to investigate the composition and physicochemical properties of dietary fibre from djulis hull. Meanwhile, determination of the in vivo antidiabetic effect on patients with type 2 diabetes mellitus (T2DM) after consuming the djulis hull powder. Djulis hull contained dietary fibre 75.21 ± 0.17% dry weight, and insoluble dietary fibre (IDF) reached 71.54 ± 0.27% dry weight. The IDF postponed the adsorption of glucose and reduced the activity of α-amylase. Postprandial blood glucose levels in patients with T2DM showed three different tendencies. First, the area under the glucose curve was significantly lower after ingesting 10 or 5 g djulis hull powder, which then postponed the adsorption of glucose, but the area under the glucose curve was similar with the two doses. After consuming 10 g djulis hull before 75 g glucose 30 and 60 min after the meal, patients with T2DM had blood glucose values that were significantly lower at the same postprandial times than those of patients who did not consume djulis hull. In short, patients who consumed djulis hull prior to glucose administration had decreased blood glucose level compared with those who did not. Djulis hull may have benefits for patients with T2DM.

12.
Inorg Chem ; 60(7): 4764-4771, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33721490

RESUMO

The reaction of Re(CO)5Cl with 4-mercaptopyridine (4-PySH) led to the formation of [Re(CO)3(4-HPyS)3]Cl (1), showing three hydrogen-bonding donors of 4-PySH ligands as well as a characteristic ligand-to-metal charge-transfer absorption at ca. 380 nm. In this regard, a variety of anions, i.e., CN-, OAc-, F-, Cl-, Br-, I-, PF6-, NO3-, ClO4-, and H2PO4-, were examined to study anion-recognition studies through hydrogen-bonding functionalities. Upon the addition of CN- to a methanolic solution of complex 1, a remarkable spectral change with an isosbestic point at ca. 314 nm in the absorption spectra was observed, with a binding constant (Kb) calculated to be 24770 M-1. Moreover, the OAc- anion also shows a similar trend, but a mild spectral change, with Kb calculated to be 2170 M-1. Unlike those of CN- and OAc-, the addition of F-, Cl-, Br-, and I- anions causes a less pronounced spectral change with an isosbestic point at ca. 350 nm and Kb calculated to be 2863-750 M-1. However, almost no spectral change can be observed for other anions (i.e., PF6-, NO3-, H2PO4-, and ClO4-). Interestingly, the molecular loops of [Re(CO)3Cl(Py2S2)]2 (2; Py2S2 = 4,4'-dipyridyl disulfide) and [Re(CO)3Cl(Py2S)0.35(Py2S2)0.65]2 (3; Py2S = 4,4'-dipyridyl sulfide) can be isolated and structurally characterized by X-ray diffraction, where those crystals were grown from diethyl ether diffusion into a methanolic solution of complex 1 with [Bu4N]CN and [Bu4N]NO3, respectively. It is noted that such unusual ligand-coupling reactions toward the homoligand and hybrid-ligand loops of complexes 2 and 3 can be achieved at room temperature in this study.

13.
Microbiol Immunol ; 64(9): 620-629, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32691886

RESUMO

The thymic microenvironment plays an important role in the development of T cells. A decrease of thymic epithelial cells is the main cause of age-related thymic atrophy or degeneration. Resveratrol (RSV), a phytoalexin produced from plants, has been shown to inhibit the adverse effects of dietary obesity on the structure and function of the thymus. D-Galactose (D-gal) can induce accelerated aging in mice. In the present study, young mice (2 months old) were injected with D-gal (120 mg/kg/day) for 8 consecutive weeks to construct an accelerated aging model. Compared with normal control mice, the thymus epithelium of the D-gal treated mice had structural changes, the number of senescent cells increased, the number of CD4+ T cells decreased, and CD8+ T cells increased. After RSV administration by gavage for 6 weeks, it was found that RSV improved the surface phenotypes of D-gal treated mice, and recovered thymus function by maintaining the ratio of CD4+ to CD8+ cells. It also indicated that RSV enhanced the cell proliferation and inhibited cell senescence. Increased autoimmune regulator (Aire) expression was present in the RSV treated mice. The lymphotoxin-beta receptor (LTßR) expression also increased. These findings suggested that RSV intake could restore the alterations caused by D-gal treatment in the thymus via stimulation of Aire expression.


Assuntos
Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Resveratrol/farmacologia , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/metabolismo , Animais , Relação CD4-CD8 , Modelos Animais de Doenças , Galactose/efeitos adversos , Regulação da Expressão Gênica , Receptor beta de Linfotoxina/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Timócitos/efeitos dos fármacos , Timo/patologia , Fatores de Transcrição/metabolismo
15.
Phytother Res ; 34(5): 1142-1153, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31985119

RESUMO

Cisplatin (DDP) is one of the first-line chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P-gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P-gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cinamatos/uso terapêutico , Cisplatino/uso terapêutico , Depsídeos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cinamatos/farmacologia , Cisplatino/farmacologia , Depsídeos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Nus , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Transl Cancer Res ; 9(2): 918-929, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35117437

RESUMO

BACKGROUND: Brucea javanica oil emulsion (BJOE) is a traditional Chinese medicine with recognized antitumor effects in various cancers, but the effects and mechanisms of action of BJOE against cervical cancer need to be further studied. Herein, we investigated the effects of BJOE on the human papillomavirus (HPV)16-expressing human cervical cancer line SiHa and explored the possible underlying mechanisms. METHODS: Cell viability and apoptosis of SiHa cells treated with BJOE were assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and annexin V-fluorescein isothiocyanate (annexin V-FITC)/propidium iodide (PI) staining assays, respectively. Quantitative reverse transcription-polymerase chain reaction and Western blot analyses were performed to assess the expression levels of the E6 oncogene and key signaling molecules involved in apoptosis. A subcutaneous xenograft nude mouse model bearing SiHa cells was established and treated with BJOE through intraperitoneal injection. Tumor growth was monitored, and immunohistochemical analysis was performed. RESULTS: BJOE exhibited substantial cytotoxic effects in SiHa cells and significantly suppressed tumor growth in SiHa cell xenografts. BJOE inhibited E6 expression and induced apoptosis in vitro in a dose-dependent manner. BJOE-induced apoptosis was characterized by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, BJOE induced phosphorylation of extracellular-signal regulated kinase (ERK) and inhibited the expression of nuclear factor-kappa B (NF-κB). CONCLUSIONS: BJOE exerts a strong tumor-suppressive effect in SiHa cells in vitro and in vivo, likely caused by E6 inhibition and apoptosis induction achieved through the ERK/mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, supporting potential use of BJOE in cervical cancer treatment.

17.
Front Cell Dev Biol ; 8: 610097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33614623

RESUMO

The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC.

18.
Zhongguo Gu Shang ; 32(11): 1008-1013, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31870048

RESUMO

OBJECTIVE: To compare clinical effects of minimally invasive percutaneous plate osteosynthesis(MIPPO) and open reduction and internal fixation under arthroscopy for the treatment of low energy tibial plateau fracture with ligament injury. METHODS: From March 2016 to March 2017, 60 tibial plateau fracture patients with ligament injury were divided into A and B groups according to random number table. In group A, there were 30 patients including 14 males and 16 females aged from 30 to 63 years old with an average of (47.25±5.36) years old; 8 patients were classified type I, 12 patients were typeII and 10 patients type III; treated by MIPPO under arthroscopy. In group B, there were 30 patients including 16 males and 14 females aged from 32 to 60 years old with an average of (43.39±4.62) years old; 10 patients were classified to type I, 11 patients were type I and 9 patients type III; treated by open reduction and internal fixation. Imaging data, length of incision, postoperative volume of drainage, intraoperative blood loss, complications, postoperative activity time and hospital stays were observed and compared. Postoperative HSS score at 18 months was used to compare recovery of knee joint function. RESULTS: Sixty patients were followed up for 12 to 24 months with average of 18 months. There were no statistical differences in tilt angle of the tibial plateau (TPA), posterior angle of tibial plateau (PA) and femoro tibial angle (FTA) between two groups at 3 days and 12 months after operation. There was no significance in width of internal joint apace before operation, while group B(6.59±0.71) mm was bigger than group A (4.25±0.65) mm after operation at 12 months. Two patients in group A occurred complications and 6 patients in group B occurred complications, and had differences between two groups(P<0.05). Length of incision, hospital stays, postoperative volume of drainage, intraoperative blood loss and postoperative activity time in group A were(5.17±1.89) cm, (2.14±0.65) weeks, (30.02±3.15) ml, (62.63±9.58) ml, (3.16±1.87)d, respectively; while in group B were(16.25±3.47) cm, (4.57±1.09) weeks, (63.75±9.84) ml, (145.89±12.61) ml, (7.86±2.14) d, respectively; and had statistical differences between two groups(P<0.05). HSS score in group A (87.68±7.39) was higher than that of in group B(69.42±5.13) at 18 months after operation (P<0.05). CONCLUSIONS: Both of MIPPO and open reduction and internal fixation under arthroscopy for low energy tibial plateau fracture with ligament injury could provide stable fixation. Open reduction and internal fixation has advantages of simple operation, but had seriously-injured, MIPPO has advantages of less trauma, good recovery of joint function, less complications and could deal with ligament and meniscus injury.


Assuntos
Artroscopia , Fraturas da Tíbia , Adulto , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Ligamentos , Masculino , Pessoa de Meia-Idade , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
19.
Chin Med J (Engl) ; 132(23): 2783-2789, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31856048

RESUMO

BACKGROUND: Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China. METHODS: We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified. RESULTS: CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort. CONCLUSIONS: Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.


Assuntos
Transplante de Pulmão/estatística & dados numéricos , China , Sobrevivência de Enxerto , Humanos , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
20.
Medicine (Baltimore) ; 98(43): e17607, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651869

RESUMO

BACKGROUND: This study aims to provide the best possible evidence-based information on the efficacy and safety of sifalimumab for treatment of skin injury (SI) caused by systemic lupus erythematosus (SLE). METHODS: In this study, electronic databases of MEDLINE, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, Global Health, WHO Global Index Medicus, Virtual Health Library, Social Care Online, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched comprehensively from inceptions to June 30, 2019 without language restrictions. We will include randomized controlled trials (RCTs) on evaluating the efficacy and safety of sifalimumab for SI caused by SLE. Two investigators will conduct study selection, data extraction, and risk of bias assessment independently. We will use RevMan 5.3 Software to perform statistical analysis. RESULTS: This study will lie in the exhaustive and systematic nature of the literature search and its methods for evaluating quality and analyzing RCTs data. Considering the controversial efficacy of the treatment for sifalimumab, this study is responsible for improving the existing evidence on the efficacy and safety of sifalimumab for SI caused by SLE. CONCLUSION: The results of this study will provide latest evidence for judging whether sifalimumab is an effective intervention for patients with SI caused by SLE or not. STUDY REGISTRATION: CRD42019148225.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Dermatopatias/tratamento farmacológico , Pele/lesões , Anticorpos Monoclonais Humanizados , Humanos , Projetos de Pesquisa , Dermatopatias/etiologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
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