scholarly journals Bone-targeted PAMAM micelle to treat bone metastases of lung cancer

2019 ◽  
Author(s):  
Shao-bo Bai ◽  
Ying Cheng ◽  
Dao-zhou Liu ◽  
Qi-feng Ji ◽  
Miao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Bone Metastases ◽  
Nude Mice ◽  
Bone Matrix ◽  
Dependent Manner ◽  
Lung Cancer Patients ◽  
Tumor Bearing

Abstract Background: Bone is a frequent site of metastasis in lung cancer patients. So far, the treatment in bone metastasis of lung cancer still has not achieved any satisfactory effects in clinic. In this paper, alendronate (ALN) was selected to be connected with PAMAM via pH sensitive cis-aconitine anhydride (CA) to prepare bone-targeted micelle (DTX@ALN-PAMAM) to treat bone metastasis of lung cancer. Results: It was discovered that DTX@ALN-PAMAM released docetaxel (DTX) and ALN in pH-dependent manner. Besides, DTX@ALN-PAMAM showed high bind affinity with bone matrix, and quickly desorbed from bone matrix in weak acidic medium due to the rupture of cis-aconitamide bond between ALN and PAMAM. The in vitro results showed that DTX@ALN-PAMAM significantly enhanced the antitumor activity of DTX and decreased bone resorption through inhibiting the formation of osteoclasts in in-vitro 3D bone metastases model of lung cancer. In addition, DTX@ALN-PAMAM accumulated at bone metastases tissues for a relatively long time in tumor-bearing nude mice, which significantly reduced the bone resorption, relieved the pain response of tumor-bearing nude mice, and delayed the growth of bone metastases. Eventually, the therapeutic effect of DTX was improved on bone metastases of lung cancer. Conclusion: ALN modified PAMAM is a new and an effective platform for the treatment of bone metastasis of lung cancer.

Bone-targeted PAMAM nanoparticle to treat bone metastases of lung cancer

Nanomedicine ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 833-849 ◽  
Author(s):  
Shao-bo Bai ◽  
Ying Cheng ◽  
Dao-zhou Liu ◽  
Qi-feng Ji ◽  
Miao Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Bone Metastases ◽  
Anticancer Activity ◽  
Therapeutic Effect ◽  
Pain Response ◽  
Solvent Evaporation Method ◽  
Metastasis Site

Aim: To prepare pH-sensitive nanoparticle composed of alendronate (ALN) and poly(amidoamine) (PAMAM) to treat bone metastases of lung cancer. Methods: The solvent evaporation method was used to prepare docetaxel (DTX)-loaded ALN-PAMAM nanoparticles (DTX@ALN-PAMAM). Results: The in vitro results showed DTX@ALN-PAMAM significantly enhanced the anticancer activity of DTX and inhibited the formation of osteoclasts. DTX@ALN-PAMAM concentrated at bone metastasis site in mice, which resulted in the suppression of bone resorption, pain response and growth of bone metastases. Eventually, the therapeutic effect of DTX on bone metastases of lung cancer was obviously improved. Conclusion: ALN modified PAMAM nanoparticle could be an effective platform for the treatment of bone metastases of lung cancer.

Usefulness of serial measurement of serum N-telopeptides of type I collogen (NTx) in patients with lung cancer who developed bone metastasis: A prospective study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18036-e18036
Author(s):  
Motohiro Tamiya ◽  
Hideaki Okada ◽  
Masashi Kobayashi ◽  
Hidekazu Suzuki ◽  
Norio Okamoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Disease Progression ◽  
Type I ◽  
Lung Cancer Patients ◽  
Serial Measurement ◽  
A Prospective Study

e18036 Background: The bone resorption biomarkers urinary NTx (uNTx) and serum NTx (sNTx) have been shown to aid in the diagnosis of bone metastasis in patients with lung cancer. Patients with metastatic bone disease from lung cancer (MBDLC) are often treated with zoledronic acid. Zoledronic acid reduces the levels of bone resorption biomarkers and also the risk of skeletal adverse events in patients with MBDLC. We studied the effects of treatments including zoledronic acid on levels of sNTx during disease progression. Methods: Patients with MBDLC at the initial diagnosis were entered to this study. sNTx was measured once a month using the sNTx assay OSTEOMARK serum NTx (Alere Medical). MBDLC was characterized by monthly physical examination and by bone scintigraphy every 3 months for 12 months. All patients were required to provide written informed consent. Results: Twenty patients were enrolled between June and December 2010. The mean +/- 1 SD of the sNTx concentrations was 19.8 +/- 5.8 nM BCE/L at baseline. In the 16 patients receiving zoledronic acid, the levels of sNTx showed a significant decrease in the first month of treatment (baseline: 21.3 +/- 5.5 nM BCE/L; one month later: 13.6 +/- 2.7 nM BCE/L; p<0.01). During follow-up period, 12 of the patients treated with zoledronic acid experienced worsening MBDLC or had died from lung cancer, and there were statistically significant differences in the levels of sNTx at baseline (19.7 +/- 4.47 nM BCE/L), at the lowest levels after the administration of zoledronic acid (11.5 +/- 2.73 nM BCE/L) and at the point of measurable disease progression or death (13.0 +/- 2.07 nM BCE/L). Conclusions: Serial measurements of sNTx in patients with MBDLC treated with zoledronic acid might predict disease progression of bone metastasis. Administration of zoledronic acid significantly decreased the level of sNTx from baseline within one month and maintained the level of sNTx lower than baseline during study periods.

Triggering receptor expressed on myeloid cells-2 (TREM-2) elicited by lung cancer cells to facilitate tumor immune evasion.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22054-e22054 ◽  
Author(s):  
Yinan Yao ◽  
Hequan Li ◽  
Yuehong Wang ◽  
Jianying Zhou
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Immune Escape ◽  
Myeloid Cells ◽  
Mice Model ◽  
Tumor Immune Escape ◽  
Normal Medium ◽  
Lung Cancer Patients ◽  
Tumor Bearing

e22054 Background: More recent evidences have argued that negative regulatory mechanism that serve to impede ongoing immune responses, which gain in interest as a complementary strategy for cancer therapy. Triggering receptor expressed on myeloid cells-2 (TREM-2) restrains phagocytosis of both dendritic cells (DCs) and macrophages(MΦs), and reduces release of inflammatory cytokines through DAP12-mediated inhibitory signal, prompting us to investigate the role of TREM-2 involved in immune dysfunction among tumor-bearing host. Methods: In lung cancer patients, monocytes of peripheral blood were analyzed by flow cytometry and MΦs around tumour cells in lung tissue were detected by immunehistochemistry. Then we prepared conditional medium containing supernatant of 3LL cells mimicing tumor microenvironment for DC and MΦ derivation, and established an orthotopic lung cancer-bearing mice model to explore the further mechanism. Results: It was showed that TREM-2 expression on monocytes was up-regulated in lung cancer patients compared with that of healthy controls, and that TREM-2 levels of macrophages had a positive correlation with TNM stage. Moreover, reduction of tumor burden, by operation or chemotherapy, led to obvious decline of TREM-2 expression. The percentage of TREM-2+DC in the murine lung significantly increased after tumor-bearing, and such DCs preformed lower MHCII-Ia, CD86 expression, and IL-12 production, but higher IL-10 secretion. In vitro, more TREM-2+DCs and TREM-2+MΦs were harvested from ‘conditional’ medium instead of ‘normal’ medium. Also, TREM-2+DCs rather than TREM-2- DCs markedly inhibited proliferation of T cells, which could be partially abolished by anti-TREM-2 mAb. Conclusions: TREM-2 acts as a negative immune regulator in promoting lung cancer progress. Our study provides new mechanism for tumor immune escape and inhibitory checkpoint for immunotherapy.

scholarly journals Lung adenocarcinoma cell-derived exosomal miR-328 promote osteoclastogenesis by targeting Nrp2

2021 ◽  
Author(s):  
Cheng Cheng Zhang ◽  
Jingru Qin ◽  
Lu Yang ◽  
Zhiyao Zhu ◽  
Xinle Qian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Bone Resorption ◽  
Lung Adenocarcinoma ◽  
Adenocarcinoma Cell ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Bone metastasis of lung cancer and detailed mechanisms are still elusive, and the roles of exosomes derived from lung adenocarcinoma cells in this process have attracted much attention. In this study, we found that lung adenocarcinoma cell-derived exosomes (LCC-Exos) promoted osteogenesis and bone resorption in vitro. Furthermore, LCC-Exos target bone in vivo and promoted bone resorption in vivo. Mechanistically, LCC-Exosomal miR-328 promoted bone resorption by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors inhibited bone resorption in vivo. Thus, LCC-Exosomal miR-328 promote osteoclastogenesis by targeting Nrp2 and LCC-ExosmiR-328 Inhibitors may serve as a potential nanomedicine for the treatment of bone metastasis.

Expression and Correlation Analysis of Clinical Pathological Characteristics of Vascular Endothelial Growth Factor, Matrix Metalloproteinases and Microvessel Density in Lung Cancer with Bone Metastasis

2019 ◽  
Vol 9 (9) ◽  
pp. 1232-1237
Author(s):  
Xuefei Qi ◽  
Hong Liu ◽  
Ruiyun Liu ◽  
Lixin Sun ◽  
Xinjuan Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Vascular Endothelial ◽  
Factor Matrix ◽  
Lung Cancer Patients ◽  
Tumor Group ◽  
Endothelial Growth Factor

Lung cancer is a common malignant tumor in clinic and easy to have bone metastases. Vascular endothelial growth factor (VEGF) is an angiogenic factor. Matrix metalloproteinases (MMPs) is associated with invasion and metastases. This study was to detect VEGF, microvessel density (MVD), MMP-2 and MMP-9 (MMP-2/9) levels in the serum and tissues of lung cancer patients with bone metastases to analyze the relaitonship between these changes and lung cancer with bone metastases. 60 patients with metastatic tumor of lung cancer were selected as experimental group, primary malignant tumor of bone and benign osteoma were regarded as control group, the contents of VEGF, MMP-2/9 in blood and tissues were analyzed by ELISA and IHC, respectively. VEGF, MVD, MMP-2/9 levels in serum and tissues of lung cancer bone metastasis group were significantly higher than that of primary bone tumor group and benign bone tumor group and their changes were significantly associated with pathological types of lung cancer, numbers and sizes of primary foci, numbers of bone metastases, other organ metastases and whether or not receiving radiotherapy and chemotherapy (P < 0.05). In conclusion, the level of VEGF, MVD, MMP-2/9 is significantly elevated in lung cancer patients with bone metastases, suggesting that these molecules might be involved in the pathogenesis of lung cancer with bone metastases.

scholarly journals MicroRNA-106a regulates autophagy-related cell death and EMT by targeting TP53INP1 in lung cancer with bone metastasis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Lei Han ◽  
Zeyong Huang ◽  
Yan Liu ◽  
Lijuan Ye ◽  
Dongqi Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Bone Metastasis ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Metastatic Progression ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients

AbstractBone metastasis is one of the most serious complications in lung cancer patients. MicroRNAs (miRNAs) play important roles in tumour development, progression and metastasis. A previous study showed that miR-106a is highly expressed in the tissues of lung adenocarcinoma with bone metastasis, but its mechanism remains unclear. In this study, we showed that miR-106a expression is dramatically increased in lung cancer patients with bone metastasis (BM) by immunohistochemical analysis. MiR-106a promoted A549 and SPC-A1 cell proliferation, migration and invasion in vitro. The results of bioluminescence imaging (BLI), micro-CT and X-ray demonstrated that miR-106a promoted bone metastasis of lung adenocarcinoma in vivo. Mechanistic investigations revealed that miR-106a upregulation promoted metastasis by targeting tumour protein 53-induced nuclear protein 1 (TP53INP1)-mediated metastatic progression, including cell migration, autophagy-dependent death and epithelial–mesenchymal transition (EMT). Notably, autophagy partially attenuated the effects of miR-106a on promoting bone metastasis in lung adenocarcinoma. These findings demonstrated that restoring the expression of TP53INP1 by silencing miR-106a may be a novel therapeutic strategy for bone metastatic in lung adenocarcinoma.

scholarly journals The homogeneous and heterogeneous risk factors for occurrence and prognosis in lung cancer patients with bone metastasis

2019 ◽  
Vol 17 ◽  
pp. 100251 ◽  
Author(s):  
Ben Wang ◽  
Lijie Chen ◽  
Chongan Huang ◽  
Jialiang Lin ◽  
Xiangxiang Pan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Lung Cancer Patients

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

scholarly journals ‘Educated’ Osteoblasts Reduce Osteoclastogenesis in a Bone-Tumor Mimetic Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 263
Author(s):  
Alexus D. Kolb ◽  
Jinlu Dai ◽  
Evan T. Keller ◽  
Karen M. Bussard
Keyword(s):  
Bone Resorption ◽  
Bone Tumor ◽  
Bone Matrix ◽  
Necrosis Factor Alpha ◽  
Tumor Bearing ◽  
Receptor Activator ◽  
Factor Alpha ◽  
Osteoclast Resorption ◽  
Necrosis Factor

Breast cancer (BC) metastases to bone disrupt the balance between osteoblasts and osteoclasts, leading to excessive bone resorption. We identified a novel subpopulation of osteoblasts with tumor-inhibitory properties, called educated osteoblasts (EOs). Here we sought to examine the effect of EOs on osteoclastogenesis during tumor progression. We hypothesized that EOs affect osteoclast development in the bone-tumor niche, leading to suppressed pre-osteoclast fusion and bone resorption. Conditioned media (CM) was analyzed for protein expression of osteoclast factors receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα) via ELISA. EOs were co-cultured with pre-osteoclasts on a bone mimetic matrix to assess osteoclast resorption. Pre-osteoclasts were tri-cultured with EOs plus metastatic BC cells and assessed for tartrate-resistance acid phosphatase (TRAP)-positive, multinucleated (≥3 nuclei), mature osteoclasts. Tumor-bearing murine tibias were stained for TRAP to determine osteoclast number in-vivo. EO CM expressed reduced amounts of soluble TNFα and OPG compared to naïve osteoblast CM. Osteoclasts formed in the presence of EOs were smaller and less in number. Upon co-culture on a mimetic bone matrix, a 50% reduction in the number of TRAP-positive osteoclasts formed in the presence of EOs was observed. The tibia of mice inoculated with BC cells had less osteoclasts per bone surface in bones with increased numbers of EO cells. These data suggest EOs reduce osteoclastogenesis and bone resorption. The data imply EOs provide a protective effect against bone resorption in bone metastatic BC.

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