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The rich morphology of 2D materials grown through chemical vapor deposition (CVD), is a distinctive feature. However, understanding the complex growth of 2D crystals under practical CVD conditions remains a challenge due to various intertwined factors. Real-time monitoring is crucial to providing essential data and enabling the use of advanced tools like machine learning for unraveling these complexities. In this study, we present a custom-built miniaturized CVD system capable of observing and recording 2D MoS2 crystal growth in real time. Image processing converts the real-time footage into digital data, and machine learning algorithms (ML) unveil the significant factors influencing growth. The machine learning model successfully predicts CVD growth parameters for synthesizing ultralarge monolayer MoS2 crystals. It also demonstrates the potential to reverse engineer CVD growth parameters by analyzing the as-grown 2D crystal morphology. This interdisciplinary approach can be integrated to enhance our understanding of controlled 2D crystal synthesis through CVD.
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Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, but the early diagnosis rate is low. The RNA-binding ubiquitin ligase MEX3C promotes tumorigenesis in several cancers but its mechanism of action in LUAD is unclear. In this study, the biological activity of MEX3C was assessed in LUAD. MEX3C and RUNX3 mRNA levels in the tissues of LUAD patients were determined using reverse transcriptionquantitative PCR. The involvement of MEX3C in the growth and metastasis of LUAD cells was measured by EdU assay, CCK-8, colony formation, Transwell assay, TUNEL, and flow cytometry. Expression of apoptosis and epithelial-mesenchymal transition related proteins were determined using western blotting analysis. LUAD cells transfected with si-MEX3C were administered to mice subcutaneously to monitor tumor progression and metastasis. We found that MEX3C is strongly upregulated in LUAD tissue sections, and involved in proliferation and migration. A549 and H1299 cells had significantly higher levels of MEX3C expression compared to control HBE cells. Knockdown of MEX3C dramatically decreased cell proliferation, migration, and invasion, and accelerated apoptosis. Mechanistically, we demonstrate MEX3C induces ubiquitylation and degradation of tumor suppressor RUNX3. Moreover, RUNX3 transcriptionally represses Suv39H1, as revealed by RNA pull-down and chromatin immunoprecipitation assays. The in vivo mice model demonstrated that knockdown of MEX3C reduced LUAD growth and metastasis significantly. Collectively, we reveal a novel MEX3C-RUNX3-Suv39H1 signaling axis driving LUAD pathogenesis. Targeting MEX3C may represent a promising therapeutic strategy against LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , MicroARNs , Animales , Humanos , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Regulación Neoplásica de la Expresión Génica , Ligasas/genética , Ligasas/metabolismo , Neoplasias Pulmonares/patología , MicroARNs/genética , ARN/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , UbiquitinaciónRESUMEN
BACKGROUND: For brain metastases (BMs) from EGFR/ALK-positive non-small cell lung cancer (NSCLC), the best time to administer tyrosine kinase inhibitors (TKIs) and brain radiotherapy (RT) has not been identified. This analysis was an attempt to solve this problem in part. METHODS: A total of 163 patients with EGFR/ALK-positive NSCLC and brain metastasis (BM) who were diagnosed between January 2017 and July 2022 were included in this study. Ninety-one patients underwent upfront RT, and 72 patients received deferred RT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. RESULTS: The average follow-up period was 20.5 months (range 2.0 to 91.9 months). The median overall survival (OS) was 26.5 months, and the median intracranial progression-free survival (iPFS) was 23.6 months. Upfront RT considerably increased the iPFS (26.9 vs. 20.2 months, hazard ratio [HR] = 5.408, P = 0.020) and OS (31.2 vs. 22.3 months, HR = 4.667, P = 0.031) compared to deferred RT. According to multivariate analysis, upfront RT was an independent risk factor for predicting iPFS (HR = 1.670, P = 0.021). Upfront RT (HR = 1.531, P = 0.044), TKI therapy (HR = 0.423, P < 0.001), and oligometastases (HR = 2.052, P = 0.021) were found to be independent risk factors for OS. CONCLUSION: This study showed that upfront RT combined with TKI treatment can significantly improve intracranial disease management and prolong survival in patients with EGFR/ALK mutations in BMs from NSCLC.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Estudios Retrospectivos , Encéfalo , Receptores ErbB , Proteínas Tirosina Quinasas ReceptorasRESUMEN
Our study aimed to explore the potential mechanisms of KIF23 regulating function in the progression of nasopharyngeal carcinoma and pinpoint novel therapeutic targets for the clinical treatment of nasopharyngeal carcinoma patients. Firstly, the mRNA and protein level of KIF23 in nasopharyngeal carcinoma was measured using quantitative real-time PCR and western blot. Then, the influence of KIF23 on tumor metastasis and growth in nasopharyngeal carcinoma was determined through the in vivo and in vitro experiments. Lastly, the regulatory mechanisms of KIF23 in nasopharyngeal carcinoma were illustrated in the chromatin immunoprecipitation assay. KIF23 was first found to be overexpressed in nasopharyngeal carcinoma samples, and its expression was associated with poor prognosis. Then, the nasopharyngeal carcinoma cell's proliferation, migration, and invasion potential could be improved by inducing KIF23 expression both in vivo and in vitro. Furthermore, androgen receptor (AR) was found to bind to the KIF23 promoter region directly and enhance KIF23 transcription. At last, KIF23 could accelerate nasopharyngeal carcinoma deterioration via activating the Wnt/ß-catenin signaling pathway. AR/KIF23/Wnt/ß-catenin pathway promotes nasopharyngeal carcinoma deterioration. Our findings could serve as a new therapeutic strategy for nasopharyngeal carcinoma in the clinical practice.
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Proteínas Asociadas a Microtúbulos , Neoplasias Nasofaríngeas , Vía de Señalización Wnt , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Androgénicos/genética , Vía de Señalización Wnt/genéticaRESUMEN
The aim of the study is to investigate the role of GPR120 on the biological behavior of esophageal cancer cells in the setting of radiation and explore the mechanism. GPR120 knockdown was fulfilled by siRNA-mediated effects in two esophageal cancer cell lines Eca109 and EC9706. Colony formation, survival fraction calculation, viable cell evaluation by cell counting kit-8 assay and cell apoptosis analysis by phycoerythrin annexin V and 7-amino-actinomycin (7-AAD) staining and the flow cytometry examination was evaluated in Eca109 and EC9706 under the treatment of different radiation dosage. The mechanisms were explored by the evaluation of the Akt pathway and apoptosis protein level. Significantly decreased GPR120 mRNA and protein after GPR120 siRNA treatment compared to control siRNA treatment. Significantly decreased colony formation was found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells at the radiation dosage of 2, 4, 6 and 8 Gy. Moreover, decreased survival fraction number with increased sensitive enhancing ratio was also found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells. Decreased cell viability and increased cell apoptosis in GPR120 siRNA-treated esophageal cancer cells. GPR120 siRNA decreased the Akt phosphorylation and anti-apoptotic Bcl-2 expression level, but increased pro-apoptotic Bim expression level in esophageal cancer cell lines. GPR120 regulated the biological behavior of the esophageal cancer cells via affecting Akt pathway and apoptosis molecules. Moreover, GPR120 siRNA combined radiation treatment could be a therapeutic choice for esophageal cancer.
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Biomarcadores de Tumor/metabolismo , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tolerancia a Radiación , Receptores Acoplados a Proteínas G/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Humanos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Receptores Acoplados a Proteínas G/genética , Células Tumorales CultivadasRESUMEN
The prognosis for patients with HER-2 negative breast cancer is currently poor, largely due to the lack of efficacious targeted therapeutics. Photodynamic nanomaterial technologies have rapidly developed in recent years, but their anti-tumor effects are often limited by poor targeting, low transformation efficiency, toxicity, and other factors. Thus, we prepared a new type of nanoparticles (Ce6/Dox@NPs-cRGD, CDNR) with cyclo(Arg-Gly-Asp-d-Phe-Cys) (c(RGDfC)) that target the ανß3 receptor. We loaded those nanoparticles (NPs) with a combination of the doxorubicin (Dox) and photosensitizer chlorin E6 (Ce6) to test synergy between chemotherapy and photodynamic therapy (PDT) for the treatment of ανß3 receptor positive and HER-2 negative breast cancer. Through analysis of the Fourier transform infrared and UV-vis spectra of these NPs, we found that Ce6 and Dox were successfully loaded into the CDNR. According to dynamic light scattering (DLS) analyses, CDNR particles had a diameter of 112.6 nm (polydispersity index 0.11), which was also confirmed via TEM characterization. The zeta potential was about -21.5 mV. Stability studies showed that CDNR particle size was stable in ddH2O, PBS, and DMEM + 5 % FBS for 16 days. The drug loading content of Dox and Ce6 were 5.3 and 6.8 %, respectively. Release studies of CDNR showed that the slow release of Dox was accelerated with increasing GSH concentration, and there was no burst release effect. From studying the absorbance of 9,10-dimethylanthrancene (ABDA), we found that CDNR produces high levels of ROS after excitation with a 670 nm laser, and ROS production increased with increasing radiation time. CDNR was significantly taken up by MCF-7 cells at 6 h because of cRGD targeting. In a CCK8 test, the relative growth rate (RGR) of CDNR +670 nm laser for MCF-7 cells was less than 75 % at 20 µg/mL after 24 h treatment and 15 µg/mL after 48 h treatment. We found that CDNR's effects on RGR were concentration dependent. Live-cell staining with a DCFH-DA kit and flow cytometry assay further supported that a CDNR +670 nm laser provided the maximum chemotherapy-PDT toxicity and production of intracellular ROS, and that cell death was mainly caused by necrosis and apoptosis. In vivo experiments showed that using the cRGD-targeting strategy, CDNR had a stronger affinity and increased half-life relative to Ce6/Dox@NPs in mice with MCF-7 xenograft tumors. Further, the Cmax of CDNR in the transplanted tumor occurred 8 h post-injection (HPI) and there was still detectable signal at 24 HPI. In addition, MCF-7 bearing mice that were treated with CDNR +670 nm PDT at 8 HPI had a significantly decreased tumor volume (P < 0.05) and prolonged survival time compared to other groups. Thus, CDNR plus 670 nm PDT was associated with favorable anti-tumor activity with no appreciable impact on body weight or the major organs in mice, as determined by immunohistochemistry/immunofluorescence and hematoxylin-eosin staining. In conclusion, CDNR with 670 nm laser irradiation represents a promising new potential treatment paradigm for the management of breast cancers that are ανß3-receptor positive and HER-2 negative.
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Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/terapia , Doxorrubicina/uso terapéutico , Integrina alfaVbeta3/genética , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/administración & dosificación , Porfirinas/uso terapéutico , Receptor ErbB-2/genética , Animales , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Clorofilidas , Terapia Combinada , Sistemas de Liberación de Medicamentos , Humanos , Nanopartículas , Tamaño de la Partícula , Especies Reactivas de Oxígeno , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lung cancer is the most frequent cancer type and is the leading cause of tumour-associated deaths worldwide. Nuclear cap-binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non-small-cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial-mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up-regulated CUL4B expression via interaction with nuclear cap-binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1-induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1-NCBP3-CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.
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Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Carcinogénesis/patología , Proteínas Cullin/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Complejo Proteico Nuclear de Unión a la Caperuza/metabolismo , Regulación hacia Arriba/genética , Animales , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas Cullin/metabolismo , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Desnudos , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Cicatrización de HeridasRESUMEN
In this study, we used folic-acid-modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) to encapsulate cisplatin and paclitaxel (separately or together), and evaluated their antitumor effects against lung cancer; this study was conducted in order to investigate the antitumor effects of the co-delivery of cisplatin and paclitaxel by a targeted drug delivery system. Blood compatibility assays and complement activation tests revealed that FA-PEG-PLGA nanoparticles did not induce blood hemolysis, blood clotting, or complement activation. The results also indicated that FA-PEG-PLGA nanoparticles had no biotoxic effects, the drug delivery system allowed controlled release of the cargo molecules, and the co-delivery of cisplatin and paclitaxel efficiently induces cancer cell apoptosis and cell cycle retardation. In addition, co-delivery of cisplatin and paclitaxel showed the ability to suppress xenograft lung cancer growth and prolong the survival time of xenografted mice. These results implied that FA-PEG-PLGA nanoparticles can function as effective carriers of cisplatin and paclitaxel, and that co-delivery of cisplatin and paclitaxel by FA-PEG-PLGA nanoparticles results in more effective antitumor effects than the combination of free-drugs or single-drug-loaded nanoparticles.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sangre/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Ácido Fólico/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas , Paclitaxel/farmacología , Poliésteres/farmacología , Polietilenglicoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Coagulación Sanguínea/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular , Cisplatino/administración & dosificación , Activación de Complemento/efectos de los fármacos , Portadores de Fármacos , Composición de Medicamentos , Ácido Fólico/administración & dosificación , Hemólisis/efectos de los fármacos , Humanos , Recuento de Leucocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/administración & dosificación , Paclitaxel/administración & dosificación , Poliésteres/administración & dosificación , Poliésteres/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Conejos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In a previous study, a novel biodegradable multiblock copolymer, monomethoxy(poly-ethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (PEAL), was developed as a new drug carrier material. It is imperative to study the biocompatibility and degradation behavior of PEAL to pave the way for clinical applications. Here, we systematically demonstrated that the PEAL copolymer has the appropriate hydrophilicity and biosafety. The degradation rate of the PEAL films was obtained by observing changes in mass, molecular weight (Mw), Mw distribution and degradation products. The degradation rate was observed to have a highly positive correlation with the pH of the medium and negative correlation with the ratio of lactic acid to glycolic acid (LA/GA). Cytotoxicity tests indicated that the degradation products of the copolymer were non-toxic to cells. In zebrafish embryos, the PEAL nanoparticles had no obvious impact on heart rate, production of reactive oxygen species, mortality, or cell apoptosis, and they were observed to have a long circulation time. Therefore, the PEAL copolymer has great potential for use as a drug carrier material.
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Portadores de Fármacos/metabolismo , Poliésteres/metabolismo , Polietilenglicoles/metabolismo , Polilisina/metabolismo , Animales , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/citología , Plaquetas/efectos de los fármacos , Línea Celular , Activación de Complemento/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidad , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/análisis , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidad , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/toxicidad , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Polietilenglicoles/toxicidad , Polilisina/química , Polilisina/farmacocinética , Polilisina/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Pez CebraRESUMEN
Inoperable lung adenocarcinoma is currently treated with platinum-based chemotherapy. However, the effectiveness of these chemotherapeutic agents is not the same for all patients. Patients either show quick chemoresistance (QCR) or delayed chemoresistance (DCR), which are defined by 87 and 242 days of progression-free survival (PFS) after initial platinum-based treatment, respectively. We found that QCR patients displayed an elevated level of serum cholesterol and that their tumors showed upregulated ABCG2 expression. We propose that chemoresistance may be attributed to cholesterol-induced ABCG2 expression and hypothesize that blocking ABCG2 may increase the efficacy of platinum-based chemotherapeutic agents. Using the MTT cell viability assay, we observed that cotreatment with ABCG2 blocker Nicardipine and platinum-based drugs Cisplatin, Oxaliplatin or Carboplatin significantly decreased cell viability of tumor cells. Importantly, our results also showed that incubating cells with cholesterol prior to chemotherapy treatment or cotreatment increased cell viability of tumor cells relative to the controls.
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Transportadoras de Casetes de Unión a ATP/genética , Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Colesterol/metabolismo , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas de Neoplasias/genética , Compuestos Organoplatinos/uso terapéutico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Adenocarcinoma/sangre , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Anciano , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , Línea Celular Tumoral , Colesterol/administración & dosificación , Colesterol/sangre , Cisplatino/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Nicardipino/administración & dosificación , Nicardipino/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Regulación hacia ArribaRESUMEN
Introduction: Lung cancer's high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy. Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections. Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments. Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.
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Cisplatino , Imiquimod , Neoplasias Pulmonares , Ratones Endogámicos C57BL , Animales , Cisplatino/farmacología , Cisplatino/química , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones , Imiquimod/química , Imiquimod/administración & dosificación , Imiquimod/farmacología , Hidrogeles/química , Apoptosis/efectos de los fármacos , Nanoestructuras/química , Terapia Fototérmica/métodos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Humanos , Temperatura , Células Dendríticas/efectos de los fármacos , Portadores de Fármacos/química , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/patologíaRESUMEN
Aim: To produce pH-responsive bionic high photothermal conversion nanoparticles actively targeting tumors for sensitizing photothermal therapy (PTT). Materials and Methods: The bionic nanoparticles (ICG-PEI@HM NPs) were prepared by electrostatic adsorption of indocyanine green (ICG) coupled to polyethyleneimine (PEI) and modified with tumor cell membranes. In vitro and in vivo experiments were conducted to investigate the efficacy of ICG-PEI@HM-mediated PTT. Results: The intelligent responsiveness of ICG-PEI@HM to pH promoted the accumulation of ICG and enhanced the PTT performance of ICG-PEI@HM NPs. Compared with free ICG, NPs exhibited great photothermal stability, cellular uptake, and active tumor targeting for PTT. Conclusion: ICG-PEI@HM NPs can enhance the efficacy of PTT and can be used as a new strategy for the construction of photothermal agents.
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Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Biónica , Neoplasias/patología , Verde de Indocianina/farmacología , Membrana Celular/patología , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , FototerapiaRESUMEN
Background: Preoperative localization is challenging due to the small diameter of pulmonary nodules or their deep location in the lung parenchyma during VATS surgery. The purpose of this study was to compare the efficacy and safety of both hook-wire and medical glue for pre-operative localization of pulmonary nodules. Methods: In the current study, 158 patients were retrospectively analyzed (January 2019 and January 2020). The patients underwent hook-wire or medical glue for pre-operative localization of pulmonary nodules. Among them, 74 patients in the hook-wire group and 84 patients in the medical glue group underwent VATS anatomic segmentectomy or wedge resection after localization of pulmonary nodules. Pre-operative localization data from all patients were compiled. Moreover, the efficacy and safety of the two methods were evaluated according to localization success rates and localization-related complications. Results: The success rate of localization in the medical glue group was 100% while 97.3% in the hook-wire group. After localization of the pulmonary nodules, the incidence of minor pneumothorax in the medical glue group (11.9%) was lower than that in the hook-wire group (37.8%) (p=0.01). The incidence of mild pulmonary parenchymal hemorrhage in the medical glue group (13.1%) was also lower than that in the hook-wire group (24.3%) (p=0.000). The mean time from the completion of localization to the start of surgery was also longer in the medical glue group than in the hook-wire group (p=0.000). The mean visual analog scale (VAS) scores after localization were higher in the hook-wire group than in the medical glue group (p=0.02). In both groups, parenchymal hemorrhage was significantly associated with the needle length in hook-wire localization and the depth of the medical glue in the lung parenchyma (p = 0.009 and 0.001, respectively). Conclusion: These two localization methods are safe and effective in pre-operative pulmonary nodule localization. The medical glue localization method had a lower risk of complications, a higher localization success rate, less pain after localization and more flexibility in the arrangement of operation time.
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Nasopharyngeal carcinoma (NPC) is a clinically multiple malignant tumor. At present, with the increase in the infection rate of Epstein-Barr virus, the incidence of nasopharyngeal carcinoma is also increasing day by day. To explore the effect of body size change on off-center cervical point and face doses in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy, in total, 100 patients with NPC from January 2019 to May 2020 in our hospital were selected for retrospective analysis, and they all received intensity-modulated radiation therapy. Bodyweight, horizontal longitudinal diameter of the odontoid process, longitudinal diameter of the third cervical spine, maximum radiation dose, and average radiation dose of normal organs in the first and last treatments were assessed, and the correlation between normal organ irradiation dose and body size was analyzed. Bodyweight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine in the last treatment were lower than those in the first treatment, with a statistically significant difference. There was no statistically significant difference in the maximum normal organ irradiation dose to the left eyeball, right eyeball, left crystalline lens, right crystalline lens, and maximum irradiation dose to optic nerve between the last treatment and the first treatment. In the last treatment, the maximum dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was higher than that in the first treatment. The average irradiation dose to the left eye bulb, right eye bulb, left lens, right lens, optic nerve in the last treatment, and that in the first treatment showed no significant difference. The average dose to the left parotid gland, right parotid gland, spinal cord, and brain stem in the last treatment was higher than that in the first treatment. The irradiation dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was significantly negatively correlated with body weight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine. After NPC radiotherapy, the body size of patients can change, which can have different effects on irradiation doses. Therefore, the target area and dose should be corrected during treatment to ensure the efficacy and safety of the treatment.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Tamaño Corporal , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/radioterapia , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios RetrospectivosRESUMEN
Subglottic small cell carcinoma (SSMCC) is a rare type of neoplasm, meaning that laryngeal cancer guidelines in several countries, including the National Comprehensive Cancer Network (NCCN) guidelines, do not include treatment principles for SSMCC. Angiogenesis is an established factor in tumor initiation, growth, and dissemination. Apatinib mesylate, an orally administered drug, is a novel inhibitor of vascular endothelial growth factor receptor-2, a key mediator of angiogenesis, and has been shown to be safe and efficacious in the treatment of certain types of malignant tumors. To the best of our knowledge, there are few reports on the treatment of SSMCC with apatinib combined with concurrent chemoradiotherapy. In the present report of SSMCC in a 64-year-old woman, oral apatinib was given daily at a dose of 250 mg in combination with concurrent chemoradiotherapy; the only toxicities reported were mild leukopenia and finger numbness. Clear and rapid efficacy was observed with the disappearance of the tumor mass. Our findings indicate that apatinib combined with concurrent chemoradiotherapy may be effective in patients with SSMCC, with adverse reactions within the manageable range, thus representing an additional treatment option for this type of malignancy.
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Carcinoma de Células Pequeñas , Neoplasias Pulmonares , Carcinoma de Células Pequeñas/tratamiento farmacológico , Quimioradioterapia , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Piridinas , Factor A de Crecimiento Endotelial VascularRESUMEN
Nasopharyngeal carcinoma (NPC) is a cancer that occurs in the nasopharynx. Infinite proliferation and distant metastasis are the main characteristics of NPC cells, and the main reason for the current failure of malignant tumor treatment. In this study, by integrating the immunohistochemical, cell transfection, western blot and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we observed that the expression of KISS1 and its receptor gene (KISS1R) negatively related with the proliferation of NPC cells. Overexpression of the KISS1 genes in cells reduced cell proliferation, slow down the cell cycle, and increased apoptosis. Additionally, overexpression of these genes significantly increased Liver Kinase B1 (LKB1), phosphorylation of LKB1 and AMPK, indicated by Western blotting. Together, all of these results suggested for the first time that KISS1 and KISS1R suppress the proliferation of NPC cells by activating the LKB1/AMPK pathway, thus revealing a viable indicator for diagnosis of NPC in clinical practice.
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INTRODUCTION: Cranial radiotherapy (CRT) is the main treatment for non-small cell lung cancer (NSCLC) with brain metastasis (BM) and non-EGFR/ALK/ROS1-TKIs indication, and anlotinib can improve overall prognosis. However, the clinical effects of CRT combined with anlotinib for the treatment of NSCLC with BM remain unclear. METHODS: We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone in NSCLC patients with BM and non-EGFR/ALK/ROS1-TKIs indication from September 2016 to June 2020. The progression-free survival (PFS) and overall survival (OS) of anlotinib + CRT versus CRT alone were analyzed. After evaluation of the clinical characteristics to generate a baseline, the independent prognostic factors for intracranial PFS (iPFS) and OS were subjected to univariate and multivariate analysis. Finally, subgroup analysis for iPFS and OS was performed to assess treatment effects using randomized stratification factors and stratified Cox proportional hazards models. RESULTS: This study included data for 73 patients with BM at baseline. Of the 73 patients, 45 patients received CRT alone, and 28 patients received CRT + anlotinib. There was no significant difference in clinical features between the two groups (P > 0.05). Compared with the CRT group, the combined group had longer iPFS (median iPFS [miPFS]: 3.0 months vs 11.0 months, P = 0.048). However, there were no significant differences in OS, extracranial PFS, and systemic PFS. For clinical features, univariate and multivariate analysis showed that the plus anlotinib treatment was an independent advantage predictor of iPFS (hazard ratio [HR] 0.51; 95% confidence interval [CI] 0.27-0.95; P = 0.04), and age ≥57 years (HR 1.04, 95% CI 1.01-1.08, P = 0.014) and KPS score ≤80 (HR 1.04, 95% CI 1.01-1.08, P = 0.014) were independent disadvantage predictors of OS (P < 0.05). In addition, although this difference was not statistically significant (p > 0.05), the patients with the anlotinib + local CRT (LCRT) treatment had the longest iPFS (miPFS: 27.0 months) and OS (median OS [mOS]: 36 months). The miPFS and mOS values for the LCRT group were 11 months and 18 months, respectively, with shorter values for whole-brain RT (WBRT) + anlotinib group, WBRT + LCRT + anlotinib group, WBRT, and WBRT + LCRT. CONCLUSION: Anlotinib can improve the intracranial lesion control and survival prognosis of NSCLC patients with CRT.
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Liposarcoma is a type of common tumor in soft tissue, but liposarcoma originating in the mediastinum is rare. Here, we report a case of the anterior mediastinal liposarcoma resected by a median sternal incision and complicated with reexpansion pulmonary edema after surgery. A 68-year-old female patient with chest tightness and shortness of breath for more than 2 years, recently presents with increased chest tightness and shortness of breath, as well as right upper extremity and lower back pain. Enhanced chest CT scan showed an uneven and low-density mass in the anterior mediastinum with clear border. Most of the mass showed fat density, the anterior part of the mass was solid, and the liquid density was seen in the pericardial cavity. Surgery was performed with a median sternal incision, and part of the pericardium and the innominate vein wall were removed during the removal of the entire liposarcoma. The size of the tumor was about 20 cm × 10 cm × 8 cm. The patient developed a reexpansion pulmonary edema after the giant mediastinal liposarcoma resection, but she was discharged successfully on the 10th postoperative day with the treatment by anti-glucocorticoids and diuretics. Postoperative pathology showed well-differentiated liposarcoma. Now within the half-year follow-up, the patient remained well and there is no sign of recurrence. Median sternotomy is considered to be a good surgical procedure for giant mediastinal liposarcomas. Attention should be given to prevent reexpansion pulmonary edema after surgery.
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OBJECTIVES: Video assisted thoracoscopic surgery (VATS) can currently be used to diagnose and treat pulmonary nodules. However, intraoperative location of pulmonary nodules in VATS is challenging due to their small diameter and deep location in the pulmonary parenchyma. The purpose of this study was to report the clinical safety and effectiveness of CT-guided hook-wire for preoperative localization of malignant pulmonary nodules smaller than 1 cm in diameter. METHODS: From February 2017 to January 2018, we collected the data of 80 patients with malignant pulmonary nodules less than 1 cm in diameter who underwent CT-guided hook-wire preoperative localization and VATS surgery. The effectiveness of preoperative localization was evaluated based on surgical duration, success rate of VATS surgery, and localization-related complications. RESULTS: The diameter of pulmonary nodules were 0.85 ± 0.17 mm with a distance to the pleural surface of 19.66 ± 14.10 mm. The length of the hook-wire in the lung parenchyma was 29.17 ± 13.14 mm and hook-wire dislodgement occurred in 2 patients. Complications included 27 cases of minor pneumothorax and 18 cases of mild parenchymal hemorrhage. A significant correlation was observed between the length of the hook-wire in the lung parenchyma and mild parenchymal hemorrhage (P = 0.044). The average time of hook-wire localization was 9.0 ± 2.6 min and the average operation time for VATS was 89.02 ± 23.35 min without conversion thoracotomy. CONCLUSIONS: CT-guided hook-wire localization of the lesion during VATS resection is safe for malignant pulmonary nodules with diameter less than 1 cm.
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Neoplasias Pulmonares/cirugía , Nódulos Pulmonares Múltiples/cirugía , Nódulo Pulmonar Solitario/cirugía , Cirugía Torácica Asistida por Video , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Tempo Operativo , Pleura/patología , Neumotórax/cirugía , Estudios Retrospectivos , Toracotomía , Tomografía Computarizada por Rayos XRESUMEN
The combination of radiotherapy and chemotherapy is a common and useful treatment mode for tumours. But traditional methods inevitably lead to a variety of side effects. A drug delivery system (DDS), which has good biocompatibility and strong anti-tumour ability, is expected to solve this problem. Studies have shown that Ce-based nanoparticles (NPs) have good radiosensitization effect through the photoelectric effect. Hence, cisplatin-loaded LiLuF4 :Ce3+scintillation NPs (NP + Cis) were first constructed in this study, which was synthesized by the crystal precipitation method and characterized by transmission electron microscopy (TEM). Subsequently, its toxicity was verified, and the radiosensitization effect and basic radiosensitization mechanism on tumour cells and tumour-bearing mice were researched. Results showed that NP + Cis triggered massive DNA damage and effectively inhibited cell viability in vitro under the exposure of X-ray irradiation (IR). Moreover, the experiments in vivo showed that the NP + Cis had higher biosafety, which could absorb enough irradiation and produce a synergistic inhibitory effect on tumours through the releasing of Cis. NP + Cis can improve the performance of DDS in chemoradiotherapy.