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1.
BMC Psychiatry ; 24(1): 369, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755543

RESUMEN

BACKGROUND: Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. METHODS: Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. RESULTS: A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. CONCLUSIONS: This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.


Asunto(s)
Trastorno Depresivo Mayor , Mapas de Interacción de Proteínas , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , Trastorno Depresivo Mayor/genética , Femenino , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Bases de Datos Genéticas , Transcriptoma/genética
2.
Am J Cancer Res ; 14(3): 1052-1070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590405

RESUMEN

Melanoma is a common and fatal cutaneous malignancy with strong invasiveness and high mortality rate. Clinically, elderly melanoma patients tend to exhibit stronger invasion ability and poorer prognosis. Given the heterogeneity of tumors, we analyzed the prognosis and risk assessment of melanoma through aging-related genes rather than age stratification. FOXM1 and CCL4 were identified to be closely associated with melanoma prognosis. Single-cell transcriptome analysis showed that FOXM1 was significantly up-regulated in tumor cells, while CCL4 was markedly elevated in immune cells. A melanoma prognostic model was constructed based on the two independent prognostic factors. This model showed a high accuracy in predicting the mortality of melanoma patients over several years. The patients in low-risk group appeared to have more immune cell infiltration and better immune therapy efficacy. Cellular experiments showed that CCL4 could promote apoptosis of melanoma cells through immune cells, and apoptosis could regulate the expression of FOXM1. In addition, the results of the spatial transcriptome and immunohistochemistry suggested that CCL4 was highly expressed in macrophages and the expression of FOXM1 in melanoma cell was negatively correlated with immune cell infiltration, especially macrophages. Here, we established a novel prognostic model for melanoma, which showed promising predictive performance and may serve as a biomarker for the efficacy of immune checkpoint inhibition therapy in melanoma patients. In addition, we explored the function of two genes in the model in melanoma.

3.
Anal Methods ; 16(18): 2948-2958, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38669009

RESUMEN

Herein, a novel type of phosphorus and iron-doped carbon dot (P,Fe-CD) with outstanding peroxidase activity and excellent fluorescence performance was hydrothermally synthesized to colorimetrically and fluorimetrically detect tannic acid (TA). In the presence of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, the P,Fe-CDs could oxidize colorless TMB to a blue oxidation product (oxTMB) resulting in an increased value of absorbance. Simultaneously, the fluorescence intensity of P,Fe-CDs at 430 nm could be quenched owing to the fluorescence resonance energy transfer (FRET) between P,Fe-CDs and the generated oxTMB. Meanwhile, after adding the TA to the system containing TMB, H2O2 and P,Fe-CDs, the value of absorbance could be decreased and the fluorescence could be recovered because of the reduction reaction between TA and oxTMB. Therefore, fluorescence intensity and value of absorbance could be applied to quantitatively detect TA with good linearities between the concentration of TA and the fluorescence intensity/value of absorbance (0.997 and 0.997 for the colorimetric signal and fluorimetric one, respectively) and low limits of detection (0.093 µmol L-1 and 0.053 µmol L-1 for the colorimetry and the fluorimetry, respectively), which was successfully applied to the detection of TA in red wines. Moreover, we applied a smartphone-assisted method to the point-of-care detection of TA with accurate results, providing a new technique for TA detection and food quality monitoring.


Asunto(s)
Carbono , Puntos Cuánticos , Taninos , Vino , Taninos/química , Vino/análisis , Carbono/química , Puntos Cuánticos/química , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Colorimetría/métodos , Peroxidasa/química , Peroxidasa/metabolismo , Límite de Detección , Transferencia Resonante de Energía de Fluorescencia/métodos , Bencidinas/química , Oxidación-Reducción , Polifenoles
4.
Artículo en Inglés | MEDLINE | ID: mdl-38528388

RESUMEN

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Sistema de Administración de Fármacos con Nanopartículas , Sistemas de Liberación de Medicamentos , Nanomedicina , Microambiente Tumoral , Nanopartículas/uso terapéutico
5.
Anal Methods ; 16(9): 1357-1362, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38344752

RESUMEN

Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situ detection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situ exosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situ exosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situ red fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 107 particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situ detection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.


Asunto(s)
Técnicas Biosensibles , MicroARNs , MicroARNs/genética , Espectrometría de Fluorescencia , ADN , Sondas de Ácido Nucleico
6.
J Cancer ; 15(6): 1523-1535, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38370371

RESUMEN

Metastasis has been one of the most important causes of death from breast cancer, and chemotherapy remains the major option for metastatic breast cancer. However, drug resistance and higher toxicity from chemotherapy have been an obstacle for clinical practice, and the combination of chemotherapy with immunotherapy has emerged as a promising treatment strategy. Here, we describe a therapy based on the combination of disulfiram (DSF) and Cu2+ with widely used cytotoxic docetaxel (DTX). DSF/Cu-induced immunogenic cell death promoted the release of type I interferon and human monocyte-induced dendritic cell maturation, which established a foundation for the combination with chemotherapy. Consequently, the combination of DSF/Cu and DTX resulted in significantly more potent anti-tumor effects in 4T1-bearing mice than in single therapy. The present study has shed new light on combining DSF/Cu-induced immune responses with traditional chemotherapeutic agents to achieve greater benefits for patients with metastasis.

8.
Transl Lung Cancer Res ; 12(11): 2330-2341, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38090524

RESUMEN

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation is the third most common EGFR-mutant form, accounting for 10-12% of all EGFR mutations in non-small cell lung cancer (NSCLC). Chemotherapy was the first-line treatment for patients with EGFR ex20ins mutation in the era when EGFR ex20ins tyrosine kinase inhibitors (EGFR ex20ins-TKIs) were inaccessible. Although EGFR ex20ins-TKIs have since then demonstrated certain efficacy, the population benefit rate is not high due to the high cost of the drug and limited benefit to the population. Therefore, the choice of treatment modality when a patient does not have access to EGFR ex20ins-TKIs or are resistant to them remains an avenue worth exploring. Case Description: In this report, we present two cases of patients with lung adenocarcinoma and EGFR ex20ins mutation. The two patients were middle-aged Asian women with no smoking history, and both had one or more metastatic lesions. Both achieved long-term clinical benefit (progression-free survival ≥12 months) after receiving combined treatment, suggesting that this is a promising treatment modality. Conclusions: To the best of our knowledge, this is the first report supporting the combination of stereotactic body radiotherapy and apatinib and camrelizumab as an effective treatment strategy in patients with advanced EGFR ex20ins-positive NSCLC who have been previously treated with chemotherapy. The therapy described in this report might serve as a potential alternative approach for clinical oncologists.

9.
Biofactors ; 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38158592

RESUMEN

The protein kinase casein kinase 2 (CK2) exerts its influence on the metabolism of three major cellular substances by phosphorylating essential protein molecules involved in various cellular metabolic pathways. These substances include hormones, especially insulin, rate-limiting enzymes, transcription factors of key genes, and cytokines. This regulatory role of CK2 is closely tied to important cellular processes such as cell proliferation and apoptosis. Additionally, tumor cells undergo metabolic reprogramming characterized by aerobic glycolysis, accelerated lipid ß-oxidation, and abnormally active glutamine metabolism. In this context, CK2, which is overexpressed in various tumors, also plays a pivotal role. Hence, this review aims to summarize the regulatory mechanisms of CK2 in diverse metabolic pathways and tumor development, providing novel insights for the diagnosis, treatment, and prognosis of metabolism-related diseases and cancers.

10.
Stroke Vasc Neurol ; 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37949480

RESUMEN

BACKGROUND: Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations (SCCMs) to eliminate the occupation and associated subsequent lifelong haemorrhagic risk. However, the timing of surgical intervention remains controversial, especially for patients in the acute stage after severe haemorrhage. METHODS: Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively reviewed. The Modified McCormick Scale (MMS) was used to evaluate neurological and disability status. All medical information was reviewed, and all patients were followed up for at least 6 months. RESULTS: A total of 279 patients were ultimately included. With regard to long-term outcomes, 110 (39.4%) patients improved, 159 (57.0%) remained unchanged and 10 (3.6%) worsened. For patients with an MMS score of 2-5 on admission, in univariate and multivariate analyses, a ≤6 weeks period between onset and surgery (adjusted OR 3.211, 95% CI 1.504 to 6.856, p=0.003) was a significant predictor of improved MMS. Among 69 patients who first presented with severe haemorrhage, undergoing surgery within 6 weeks of the onset of severe haemorrhage (adjusted OR 4.901, 95% CI 1.126 to 21.325, p=0.034) was significantly associated with improvement of MMS score. CONCLUSION: Surgical timing can influence the long-term outcome of SCCMs. For patients with symptomatic SCCMs, especially those with severe haemorrhage, early surgical intervention within 6 weeks can provide more benefit.

11.
Technol Health Care ; 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37840511

RESUMEN

BACKGROUND: Beamforming is vital for medical ultrasound imaging systems. The generalized sidelobe canceller (GSC) beamforming can improve the image quality of lateral resolution, but its performance improvement in contrast and robustness is limited. OBJECTIVE: This paper proposes an improved generalized sidelobe canceller algorithm based on multi-apodization with cross-correlation (MAXB-IGSC), which aims to improve the contrast and robustness of ultrasound imaging while maintaining the high image resolution and background speckle quality of GSC. METHODS: The proposed MAXB-IGSC uses multiple pairs of complementary received apodization functions to process the echo data individually to obtain multiple pairs of data sets. The average of their normalized cross-correlation coefficients is then calculated and utilized to determine the adaptive subarray length of the GSC covariance matrix and weights the output of the improved GSC. RESULTS: The MAXB-IGSC improves the contrast ratio (CR) by 171.18% in anechoic cyst simulation and by 91.23%/130.97%/171.76% in geabr_0 (a dataset from the University of Michigan) experiment compared with GSC, respectively. Furthermore, MAXB-IGSC exhibits significant noise immunity, which greatly improves the robustness of the imaging. The technology also maintains the brightness and uniformity of the background speckle. CONCLUSION: The proposed MAXB-IGSC has potential for obtaining high-quality ultrasound images in clinical applications.

12.
Discov Oncol ; 14(1): 103, 2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37326784

RESUMEN

More than 60 years ago, disulfiram (DSF) was employed for the management of alcohol addiction. This promising cancer therapeutic agent inhibits proliferation, migration, and invasion of malignant tumor cells. Furthermore, divalent copper ions can enhance the antitumor effects of DSF. Molecular structure, pharmacokinetics, signaling pathways, mechanisms of action and current clinical results of DSF are summarized here. Additionally, our attention is directed towards the immunomodulatory properties of DSF and we explore novel administration methods that may address the limitations associated with antitumor treatments based on DSF. Despite the promising potential of these various delivery methods for utilizing DSF as an effective anticancer agent, further investigation is essential in order to extensively evaluate the safety and efficacy of these delivery systems.

13.
Ultrasonics ; 134: 107084, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37352574

RESUMEN

In this paper, an ultrasound imaging method combined with low-complexity adaptive beamformer (LCA) and improved multiphase apodization with cross-correlation (IMPAX) is proposed to improve image resolution and contrast with low hardware cost. Firstly, the delayed echo signal is apodized by the LCA to obtain a narrow mainlobe width echo signal and LCA output. Then, multiple pairs of complementary square-wave phase apodizations are applied to the apodized echo signal to obtain corresponding signal pairs, which are used to calculate the normalized cross-correlation (NCC) matrix. Finally, the average value of the NCC matrices is filtered by 2-D means, and the filtered result is introduced as the weighting factor for the LCA output. The simulation and experimental results show that the proposed LCA-IMPAX can effectively reduce the mainlobe width, suppress clutter, and be robust to noise. Compared with DAS, LCA, and MPAX, for simulated point targets, the full-width at half-maximum (FWHM, -6dB) of LCA-IMPAX is reduced by 49.22%, 10.06%, and 48.67%, respectively. For simulated cyst, the CR is improved by 219.91%, 138.08%, and 103.44%, respectively. For experimental cysts, the CR is improved by an average of 145.00%, 136.14%, and 55.09%, respectively. The results of human heart data indicate that LCA-IMPAX has good imaging quality in vivo. Since the proposed method does not involve covariance matrix inversion, it can be applied in real-time imaging systems.

14.
Open Life Sci ; 18(1): 20220600, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215501

RESUMEN

Thymomas and thymic carcinomas are rare and primary tumors of the mediastinum which is derived from the thymic epithelium. Thymomas are the most common primary anterior mediastinal tumor, while ectopic thymomas are rarer. Mutational profiles of ectopic thymomas may help expand our understanding of the occurrence and treatment options of these tumors. In this report, we sought to elucidate the mutational profiles of two ectopic thymoma nodules to gain deeper understanding of the molecular genetic information of this rare tumor and to provide guidance treatment options. We presented a case of 62-year-old male patient with a postoperative pathological diagnosis of type A mediastinal thymoma and ectopic pulmonary thymoma. After mediastinal lesion resection and thoracoscopic lung wedge resection, the mediastinal thymoma was completely removed, and the patient recovered from the surgery and no recurrence was found by examination until now. Whole exome sequencing was performed on both mediastinal thymoma and ectopic pulmonary thymoma tissue samples of the patient and clonal evolution analysis were further conducted to analyze the genetic characteristics. We identified eight gene mutations that were co-mutated in both lesions. Consistent with a previous exome sequencing analysis of thymic epithelial tumor, HRAS was also observed in both mediastinal lesion and lung lesion tissues. We also evaluated the intratumor heterogeneity of non-silent mutations. The results showed that the mediastinal lesion tissue has higher degree of heterogeneity and the lung lesion tissue has relatively low amount of variant heterogeneity in the detected variants. Through pathology and genomics sequencing detection, we initially revealed the genetic differences between mediastinal thymoma and ectopic thymoma, and clonal evolution analysis showed that these two lesions originated from multi-ancestral regions.

15.
J Dermatol ; 50(7): 856-868, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37020415

RESUMEN

The pathogenesis of granulomatous rosacea (GR), the only variant of rosacea, is unclear. To investigate the differences between GR and non-granulomatous rosacea (NGR) in clinical characteristics, histopathological changes and gene expression for the purpose of providing new ideas on the pathogenesis of rosacea. A total of 30 GR and 60 NGR patients were included. Their clinical and histopathological information was collected retrospectively, and the characteristics of immune cell infiltration were investigated by multiple immunohistochemical staining. RNA sequencing and transcriptome analysis were performed on three pairs of skin samples from GR and NGR patients, respectively. Then, the expressions of candidate genes that were potentially associated with granuloma formation were verified by immunohistochemical staining. It was found that GR patients were more prone to the occurrence of rosacea in the forehead, periocular and perioral skin (p = 0.001, p < 0.001, p = 0.001), and presented more severe papules and pustules when compared with NGR patients (p = 0.032). For histopathological features, the inflammatory cells primarily infiltrated around hair follicles in the GR group and around blood vessels in the NGR group. In addition, the neutrophils were richer (p = 0.036) and the expression levels of CD4+ , CD8+ and CD68+ cells were higher (p = 0.047, p < 0.001, p < 0.001) in the GR group than in the NGR group. In addition, the GR group had apparent collagen hyperplasia (p = 0.026). A total of 420 differentially expressed genes (DEGs) were detected, and bioinformatics analysis showed that the DEGs were enriched in neutrophil activation, adaptive immune response and other biological processes. Lastly, the candidate genes related to neutrophil activation and collagen hyperplasia, i.e., Cathepsin S (CTSS), Cathepsin Z (CTSZ) and matrix metalloproteinases 9 (MMP9), were confirmed to be highly expressed in the GR group. The clinical and histopathological features of GR exhibited a very diverse pattern compared with NGR, and the underlying mechanisms may be related to neutrophil activation and collagen hyperplasia.


Asunto(s)
Pueblos del Este de Asia , Rosácea , Humanos , Hiperplasia/patología , Neutrófilos/inmunología , Estudios Retrospectivos , Rosácea/etnología , Rosácea/genética , Rosácea/inmunología , Rosácea/patología , Piel/patología
16.
Cancer Med ; 12(2): 983-994, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35861052

RESUMEN

Vesicles, also known as "microparticles", are vesicle-like structures that are released outside the cell in a "sprouting" manner when the cytoskeleton is changed during cell activation or apoptosis, with a diameter of about 100-1000 nm, and are carriers of material information exchange between cells. Tumor-derived extracellular vesicles can effectively deliver drugs to the nucleus of tumor stem cells, thus effectively killing them without toxic side effects. The underlying mechanism involves the soft nature of tumor stem cells that allows better uptake of vesicles, and the entry of drug-carrying vesicles into lysosomes and facilitation of lysosomal movement toward the nucleus to deliver drugs to the nucleus. Drug-loaded vesicles have unique advantages, such as low immunogenicity, homing targeting ability, and the ability to break through the physiological barrier to tumor therapy. Tumor-derived drug-delivery vesicles have entered clinical trials for the treatment of malignant pleural effusions. In this review, we summarized the progress of basic and clinical research on tumor cell-derived drug-loaded vesicles for the treatment of malignant pleural effusion in recent years.


Asunto(s)
Micropartículas Derivadas de Células , Vesículas Extracelulares , Neoplasias Pulmonares , Derrame Pleural Maligno , Humanos , Derrame Pleural Maligno/patología , Neoplasias Pulmonares/patología , Vesículas Extracelulares/patología , Micropartículas Derivadas de Células/patología , Apoptosis
17.
Front Oncol ; 12: 1065027, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36530985

RESUMEN

Protein kinase CK2, a conserved serine/threonine-protein kinase, is ubiquitous in cells and regulates various intracellular processes, especially in tumor cells. As one of the earliest discovered protein kinases in humans, CK2 plays a crucial role in phosphorylating or associating with hundreds of substrates to modulate several signaling pathways. Excellent reviews have reported that the overexpression of CK2 could be observed in many cancers and was closely associated with tumor occurrence and development. The elevation of CK2 is also an indicator of a poor prognosis. Recently, increasing attention has been paid to the relationship between CK2 and tumor immunity. However, there is no comprehensive description of how CK2 regulates the immune cells in the tumor microenvironment (TME). Also, the underlying mechanisms are still not very clear. In this review, we systematically summarized the correlation between CK2 and tumor immunity, primarily the effects on various immune cells, both in innate and adaptive immunity in the TME. With the comprehensive development of immunotherapy and the mounting transformation research of CK2 inhibitors from the bench to the clinic, this review will provide vital information to find new treatment options for enhancing the efficacy of immunotherapy.

18.
J Acoust Soc Am ; 152(2): 921, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36050163

RESUMEN

In this paper, we propose a dual projection generalized sidelobe canceller (DPGSC) based on mixed subspace (MS) for ultrasound imaging, which aims to improve the speckle signal-noise-ratio (sSNR) and decrease the dark-region artifacts. A mixed signal subspace based on the correlation between the desired steering vector and the eigenvectors is constructed to further optimize the desired steering vector and the final weight vector. The simulated and experimental results show that the proposed method can greatly improve the speckle uniformity. In the geabr_0 experiment, the standard deviation of background and sSNR of MS-DPGSC can be improved by 48.07% and 58.49% more than those of eigenspace-based generalized sidelobe canceller (ESGSC). Furthermore, for a hyperechoic target, the maximal improvement of contrast ratio is 95.29%. In terms of anechoic cyst, the contrast-to-noise ratio of MS-DPGSC is increased by 123.08% than that of ESGSC. The rat mammary tumor experimental data show that the proposed method has better comprehensive imaging effect than traditional generalized sidelobe cancellers and ESGSCs.


Asunto(s)
Algoritmos , Artefactos , Animales , Fantasmas de Imagen , Ratas , Relación Señal-Ruido , Ultrasonografía/métodos
19.
Cell Death Dis ; 13(7): 636, 2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35864117

RESUMEN

The efficacy of apatinib has been confirmed in the treatment of solid tumors, including non-small-cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by apatinib and the precise mechanisms of drug resistance are largely unknown. In this study, we demonstrated that apatinib could reprogram glutamine metabolism in human NSCLC via a mechanism involved in amino acid metabolic imbalances. Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2α/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. Moreover, knockdown of ATF4 enhanced the antitumor effect of apatinib both in vitro and in vivo. In summary, this study showed that apatinib could reprogram glutamine metabolism through the activation of the AAR pathway in human NSCLC cells and indicated that targeting ATF4 is a potential therapeutic strategy for relieving apatinib resistance.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sistema de Transporte de Aminoácidos ASC/metabolismo , Aminoácidos/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Glutamina/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Antígenos de Histocompatibilidad Menor/metabolismo , Piridinas
20.
Eur J Pharm Sci ; 174: 106187, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35430381

RESUMEN

Cisplatin (DDP), a first-line chemo-drug for cervical cancer therapy, has limited the clinical use due to its high-dose administration and strong side effects. In this study, estrone-targeted PEGylated Liposomal DDP (ES-SSL-DDP) was prepared by thin-film hydration method and characterized. ES-SSL-DDP presented a spherical structure, with a particle size of about 97.3 nm, a surface charge of -19 mV and a high encapsulation efficiency of 47.7%. ES-SSL-DDP showed higher stability with a lower leakage rate less than 10% at 4°C. In vitro cellular uptake and internalization mechanisms in HeLa cells showed that ES-SSL-DDP had a stronger cellular uptake which was mainly via caveolin-mediated endocytosis. In vivo targeting evaluation demonstrated ES-SSL-DDP could specifically accumulated into the tumor site of HeLa-bearing mice. Cytotoxicity test on HeLa cells demonstrated the stronger cytotoxic activity of ES-SSL-DDP by MTT assay. In vivo anti-tumor efficacy of ES-SSL-DDP in HeLa tumor-bearing mice exhibited the most effective tumor inhibition. Pharmacokinetics and biodistribution of ES-SSL-DDP presented an improved metabolic behavior of the DDP. The acute toxicity demonstrated that ES-SSL-DDP could increase the LD50 and reduce the myelosuppression in healthy ICR mice. ES-SSL-DDP could be a novel promising chemo-formulation for cervical cancer in the future clinic.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias del Cuello Uterino , Animales , Antineoplásicos/química , Línea Celular Tumoral , Cisplatino/uso terapéutico , Estrona/metabolismo , Femenino , Células HeLa , Humanos , Liposomas/química , Ratones , Ratones Endogámicos ICR , Nanopartículas/química , Polietilenglicoles/metabolismo , Distribución Tisular , Neoplasias del Cuello Uterino/tratamiento farmacológico
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