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Total 18 results found since Jan 2013.

Indolyl-chalcone derivatives trigger apoptosis in cisplatin-resistant mesothelioma cells through aberrant tubulin polymerization and deregulation of microtubule-associated proteins
DiscussionCIT-026 and CIT-223 are highly effective inducers of tumor cell apoptosis by disrupting microtubule assembly, with only modest effects on non-malignant cells. CITs are potent anti-tumor agents against MPM cells, in particular cells resistant to standard therapeutics, and thus warrant further evaluation as potential small-molecule therapeutics in MPM.
Source: Frontiers in Oncology - May 25, 2023 Category: Cancer & Oncology Source Type: research

Study on co-delivery of pemetrexed disodium and Bcl-2 siRNA by poly- γ-glutamic acid-modified cationic liposomes for the inhibition of NSCLC
Drug Dev Ind Pharm. 2023 Feb 20:1-18. doi: 10.1080/03639045.2023.2182125. Online ahead of print.ABSTRACTDue to the complexity of pathophysiology of non-small cell lung cancer (NSCLC) and susceptibility of single chemotherapy to drug resistance, the combination of drugs and small interfering RNA (siRNA) may produce desired therapeutic effect on NSCLC through action of multiple pathways. We designed to develop poly-γ-glutamic acid-modified cationic liposomes (γ-PGA-CL) to co-deliver pemetrexed disodium (PMX) and siRNA to treat NSCLC. Firstly, γ-PGA was modified on surface of PMX and siRNA co-loaded cationic liposomes by e...
Source: Drug Development and Industrial Pharmacy - February 21, 2023 Category: Drugs & Pharmacology Authors: Huang Xiaoyu Song Ruonan Wang Xiao Kongfang He Rumeng Shan Xie Fei Guihua Huang Source Type: research

Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways
CONCLUSIONS: Picropodophyllin may offer novel therapeutic properties for treating acquired pemetrexed-resistant MPM. Targeting tubulin may be an important strategy in the treatment of MPM after the discontinuation of pemetrexed.PMID:35529797 | PMC:PMC9073748 | DOI:10.21037/tlcr-21-765
Source: Cell Research - May 9, 2022 Category: Cytology Authors: Rong Sun Ryosuke Tanino Xuexia Tong Eshat Fahmida Haque Yoshihiro Amano Takeshi Isobe Yukari Tsubata Source Type: research

Alterations in BAP1 are Associated with Cisplatin Resistance Through Inhibition of Apoptosis in Malignant Pleural Mesothelioma (MPM).
CONCLUSIONS: Alterations in BAP1 in MPM were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision. PMID: 33547197 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - February 5, 2021 Category: Cancer & Oncology Authors: Oehl K, Vrugt B, Wagner U, Kirschner MB, Meerang M, Weder W, Felley-Bosco E, Wollscheid B, Bankov K, Demes MC, Opitz I, Wild PJ Tags: Clin Cancer Res Source Type: research

Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients
ConclusionsThe use of peripheral blood samples for expression quantification of interest genes is an affordable method with promising results in the evaluation of response to pemetrexed treatment. Therefore, expression levels ofREV3L andTYMS genes might be used as predictive biomarkers in advanced NSCLC patients.
Source: Cancer Chemotherapy and Pharmacology - December 11, 2019 Category: Cancer & Oncology Source Type: research

FGF2-FGFR1 pathway activation together with thymidylate synthase upregulation is induced in pemetrexed-resistant lung cancer cells.
Authors: Miura K, Oba T, Hamanaka K, Ito KI Abstract Pemetrexed (MTA) is a folate antimetabolite used for treating non-small cell lung cancer. To elucidate the mechanisms of pemetrexed resistance in lung cancer, we established pemetrexed-resistant sublines in PC9 (mutant EGFR) and H1993 (wild-type EGFR) lung adenocarcinoma cell lines (PC9-MTA, H1993-MTA). Gene expression profile comparison by microarray analyses revealed enhanced fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1) expression, confirmed by Western blotting, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reacti...
Source: Oncotarget - March 7, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The arginine methyltransferase PRMT5 and PRMT1 distinctly regulate the degradation of anti-apoptotic protein CFLARL in human lung cancer cells.
CONCLUSIONS: PRMT5 and PRMT1 mediate the distinct effects on CFLARL degradation by regulating the binding of E3 ligase ITCH in NSCLC cells. This study identifies a cell death mechanism that is fine-tuned by PRMT1/5 that modulate CFLARL degradation in human NSCLC cells. PMID: 30736843 [PubMed - in process]
Source: Clinical Lung Cancer - February 8, 2019 Category: Cancer & Oncology Authors: Li M, An W, Xu L, Lin Y, Su L, Liu X Tags: J Exp Clin Cancer Res Source Type: research

Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.
In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 (SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC...
Source: Oncotarget - April 25, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Role of proton-coupled folate transporter in pemetrexed resistance of mesothelioma: clinical evidence and new pharmacological tools
ConclusionsThese findings identify for the first time PCFT as a novel mesothelioma prognostic biomarker, prompting prospective trials for its validation. Moreover, preclinical data suggest that targetingPCFT-promoter methylation might eradicate pemetrexed-resistant cells characterized by low-PCFT expression.
Source: Annals of Oncology - September 7, 2017 Category: Cancer & Oncology Source Type: research

Astrocyte-elevated gene-1 confers resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase expression.
In conclusion, our data demonstrated that TS expression might be regulated by AEG-1 and that increased expression of these proteins contributes to lung cancer disease progression and may be associated with the development of resistance to pemetrexed. PMID: 28700347 [PubMed - as supplied by publisher]
Source: Oncotarget - July 14, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Astaxanthin enhances pemetrexed-induced cytotoxicity by downregulation of thymidylate synthase expression in human lung cancer cells
In this study, we showed that down-regulating of TS expression in two NSCLC cell lines, human lung adenocarcinoma H1650 and squamous cell carcinoma H1703 cells, with astaxanthin were associated with decreased MKK1/2-ERK1/2 activity. Enforced expression of constitutively active MKK1 (MKK1-CA) vector significantly rescued the decreased TS mRNA and protein levels in astaxanthin-treated NSCLC cells. Combined treatment with a MKK1/2 inhibitor (U0126 or PD98059) further decreased the TS expression in astaxanthin-exposed NSCLC cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting ERK1/2 activity enhanced the c...
Source: Regulatory Toxicology and Pharmacology - October 1, 2016 Category: Toxicology Source Type: research

Pemetrexed + Sorafenib lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling.
Authors: Booth L, Roberts JL, Tavallai M, Chuckalovcak J, Stringer DK, Koromilas AE, Boone DL, McGuire WP, Poklepovic A, Dent P Abstract In the completed phase I trial NCT01450384 combining the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib it was observed that 20 of 33 patients had prolonged stable disease or tumor regression, with one complete response and multiple partial responses. The pre-clinical studies in this manuscript were designed to determine whether [pemetrexed + sorafenib] -induced cell killing could be rationally enhanced by additional signaling modulators. Multiplex assays performe...
Source: Oncotarget - March 27, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of autophagy potentiates pemetrexed and simvastatin-induced apoptotic cell death in malignant mesothelioma and non-small cell lung cancer cells
In this study, we determined whether autophagy could be induced by pemetrexed and simvastatin cotreatment in malignant mesothelioma and NSCLC cells. Furthermore, we determined whether inhibition of autophagy drives apoptosis in malignant mesothelioma and NSCLC cells. Malignant mesothelioma MSTO-211H and A549 NSCLC cells were treated with pemetrexed and simvastatin alone and in combination to evaluate their effect on autophagy and apoptosis. Cotreatment with pemetrexed and simvastatin induced greater caspase-dependent apoptosis and autophagy than either drug alone in malignant mesothelioma and NSCLC cells. 3-Methyladenine (...
Source: European Respiratory Journal - October 30, 2015 Category: Respiratory Medicine Authors: Kim, H.-R., Cho, K.-H., Hwang, K.-E., Jeong, E.-T. Tags: 11.1 Lung Cancer Source Type: research