Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Gabr, Adel; Goto, Hisatsugu; Hashimoto, Masaki; Ogawa, Hirohisa; Kuramoto, Takashi; Suzuki, Minako; Saijo, Atsuro; Kakiuchi, Soji; Sakaguchi, Satoshi; Moriya, Yoichiro; Sone, Saburo; Nishioka, Yasuhiko

doi:10.1007/s10585-011-9443-3

Cited by 7 publications

(3 citation statements)

References 37 publications

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“…Garfield indicated that TKIs could decrease the secretion of growth factor and RANKL, and thus induced the differentiation of osteoblast and inhibited the proliferation and activity of osteoclast [ 22 , 23 ]. Similar results were shown in SCLC cell lines [ 24 ] and prostate cancer cell lines [ 25 ].…”

Section: Discussionsupporting

confidence: 86%

Epidermal growth factor receptor is associated with the onset of skeletal related events in non-small cell lung cancer

et al. 2017

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BackgroundBone metastasis and skeletal related events (SREs) are common in non-small cell lung cancer (NSCLC). Patients with mutant epidermal growth factor receptor (EGFR) could benefit from tyrosine kinase inhibitors (TKIs). However, it is unclear whether SRE is influenced by EGFR status. We aimed to evaluate the correlation of EGFR status and TKIs with the incidence of SREs.MethodsWe conducted a retrospective study of stage IV NSCLC patients with bone metastasis. Incidence rate of SREs was collected and was compared using chi-square test. Logistic-regression analysis was used to identify the risk factors predicting the incidence of SREs.Results410 eligible patients were enrolled in the study. 49.0% were detected with EGFR mutation. 49.8% of patients received EGFR-TKIs therapy prior to the onset of SREs. 42.7% experienced at least one SRE. Patients who were treated with TKIs held lower incidence of SREs than patients who were not treated with TKIs (23.5% vs 61.7%, p<0.001). Multivariate analysis showed that poor performance status (OR 5.550, 95%CI 2.290-13.450; p<0.001) and mutant EGFR (OR 3.050, 95%CI 1.608-5.787, p=0.001) were independent risk factors predicting the onset of SREs, while the usage of TKIs (OR 0.102, 95%CI 0.054-0.193, p<0.001) was a protective factor of SREs in NSCLC patients with bone metastasis.ConclusionsThis study indicates that the incidence of SREs is common in both patients with and without EGFR mutation. Poor performance ability and mutant EGFR imply higher risks of SREs, while the usage of TKIs may be a protective factor of SREs.

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Section: Discussionsupporting

confidence: 86%

Epidermal growth factor receptor is associated with the onset of skeletal related events in non-small cell lung cancer

et al. 2017

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“…Cell migration was determined as previously described (21). Invasion assay was conducted using Matrigel-coated transwell chambers (BD Biosciences) according to the manufacturer's protocols.…”

Section: Migration and Invasion Assaymentioning

confidence: 99%

Dll4-Fc, an Inhibitor of Dll4-Notch Signaling, Suppresses Liver Metastasis of Small Cell Lung Cancer Cells through the Downregulation of the NF-κB Activity

Kuramoto

Goto

Mitsuhashi

et al. 2012

Molecular Cancer Therapeutics

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Notch signaling regulates cell-fate decisions during development and postnatal life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch signaling between cancer cells, or how this signaling affects cancer metastasis. We, therefore, assessed the role of Dll4-Notch signaling in cancer metastasis. We generated a soluble Dll4 fused to the IgG1 constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch signaling and introduced it into human small cell lung cancer (SCLC) cell lines expressing either high levels (SBC-3 and H1048) or low levels (SBC-5) of Dll4. The effects of Dll4-Fc on metastasis of SCLC were evaluated using a mouse model. Although Dll4-Fc had no effect on the liver metastasis of SBC-5, the number of liver metastasis inoculated with SBC-3 and H1048 cells expressing Dll4-Fc was significantly lower than that injected with control cells. To study the molecular mechanisms of the effects of Dll4-Fc on liver metastasis, a PCR array analysis was conducted. Because the expression of NF-kB target genes was affected by Dll4-Fc, we conducted an electrophoretic mobility shift assay and observed that NF-kB activities, both with and without stimulation by TNF-a, were downregulated in Dll4-Fc-overexpressing SBC-3 and H1048 cells compared with control cells. Moreover, Dll4-Fc attenuates, at least in part, the classical and alternative NF-kB activation pathway by reducing Notch1 signaling. These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of SCLC by regulating NF-kB signaling.

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“…Due to these adverse effects, many people may be prescribed a lower dose. [5][6][7] Biorelevant dissolution media(s) are utilized as an in vitro technique for evaluating oral formulations' in vivo performance. Biorelevant dissolving media aids in accurately mimicking physiological in vivo and in vitro conditions.…”

Section: Original Articlementioning

confidence: 99%

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2022

AJP

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Aim:The aim of the present work was to predict the bioavailability (BA) of poorly soluble drug. In vitro dissolution of selected BCS Class II drug was conducted in different dissolution media to identify the discriminatory behaviors of the dissolution media. Further, the development of physiology-based pharmacokinetic modeling performed using GastroPlus ® for BA predictions of formulation showing enhanced dissolution. Study Design: Using GastroPlus® software (Simulations Plus, Lancaster, CA), a physiology-based pharmacokinetic model for erlotinib was developed. Erlotinib absorption was described using the advanced compartmental absorption and transit model. The input parameters for the simulation were either determined experimentally or gathered from the literature. Place and Duration of Study: Amity Institute of Pharmacy, Noida. Methodology: In vitro dissolution studies were conducted and data were analyze to find the biorelevent dissolution media. GastroPlus ® model was built to predict the C max and AUC and also was validated for the prediction error <10%. Validated model was used to predict the BA parameters of optimized formulation using the dissolution profile. Results: Based on predicted T/R ratio, it is observed that optimized formulation shows approximately ~ 25% higher rate of absorption and bioavailability. Conclusion: Erlotinib tablet formulation was prepared using micronized drug substance, optimized formulation was subjected to various dissolution tests and biorelevent media was identified based on best fit/correlation with the deconvulated profile, which was further used for simulation modeling and BA prediction. Micronization can be used as a technique to enhance the drug dissolution of BCS Class II drugs and corresponding BA. IVIVR GastroPlus modeling and simulations can be useful tool to assess the biopharmaceutical performance for initial screening and further taking up the optimized formulation for clinical studies.

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Erlotinib prevents experimental metastases of human small cell lung cancer cells with no epidermal growth factor receptor expression

Cited by 7 publications

References 37 publications

Epidermal growth factor receptor is associated with the onset of skeletal related events in non-small cell lung cancer

Epidermal growth factor receptor is associated with the onset of skeletal related events in non-small cell lung cancer

Dll4-Fc, an Inhibitor of Dll4-Notch Signaling, Suppresses Liver Metastasis of Small Cell Lung Cancer Cells through the Downregulation of the NF-κB Activity

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