scholarly journals Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 294 ◽  
Author(s):  
Chishti ◽  
Dhamecha ◽  
Jalalpure ◽  
Dehghan
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pulmonary Delivery ◽  
Small Cell ◽  
Small Cell Lung ◽  
Dry Powder ◽  
Term Delivery

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around −36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

scholarly journals Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Osteoclast Differentiation ◽  
Small Cell ◽  
Signalling Pathway ◽  
Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

scholarly journals Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo

Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preparation And Evaluation

Cytogenetic Findings in Primary Non-Small Cell Lung Cancer

1994 ◽  
Vol 80 (2) ◽  
pp. 151-156
Author(s):  
Elvira D'Alessandro ◽  
Maria Luisa Lo Re ◽  
Roberto Crisci ◽  
Claudio Ligas ◽  
Giorgio Furio Coloni
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Chromosome Loss ◽  
Small Cell Lung ◽  
Primary Nsclc ◽  
Cytogenetic Analyses ◽  
Triploid Clone

Non-small cell lung cancer (NSCLC) shows a complex cytogenetic heterogeneity and up to now no particular chromosomal aberration seems to characterize its malignant evolution. We therefore performed cytogenetic analyses of 20 primary NSCLC, 8 adenocarcinomas and 12 squamous cell carcinomas on direct preparations or short-term cultures. Only 1 case was analyzed after long-term culture. Results were obtained from 11 samples and clonal rearrangements were found in 3 cases, a diploid and a near-triploid clone with several aberrations such as i (9q), rob (14; 15) and rob (21; 21) in 1 case, a near-triploid clone in 1 case, and Y chromosome loss in 1 case. Other aberrations found were sporadic, but + 7 aneuploidy and translocations involving 1p were detected in 2 and 3 samples respectively. Although to date it has been very difficult to recognize primary changes in NSCLC, nevertheless a literature review and our results indicate that i(9q) and robertsonian translocations are relevant findings.

scholarly journals Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

2018 ◽  
Vol 45 (6) ◽  
pp. 2213-2224 ◽  
Author(s):  
Meng Zhao ◽  
Yahui Liu ◽  
Ran Liu ◽  
Jin Qi ◽  
Yongwang Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

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