sodium-glycididazole and Lung-Neoplasms

Median survival of patients with brain metastases from non-small cell lung cancer is poor. This study was to investigate the radiation-enhancing effect of sodium glycididazole combined with whole-brain radiotherapy of multiple brain metastases from non-small cell lung cancer.. Sixty-four patients with multiple brain metastases from non-small cell lung cancer were included: the study group (n=32) received whole-brain radiotherapy combined with sodium glycididazole at a dose of 700mg/m(2) intravenous infusion 30minutes before radiotherapy, three times a week; the control group (n=32) only received whole-brain radiotherapy. The primary end point was central nervous system (CNS) progression-free survival and overall survival. The treatment-related toxicity was also recorded.. The CNS disease control rate was better (90.6% vs 65.6%, P=0.016) in the study group than in the control group at 3 month of follow-up. The median CNS progression-free survival time was longer in the study group than in the control group (7.0 months vs 4.0 months, P=0.038). There was no significant difference of the median overall survival time between the study group and the control group (11.0 months vs 9.0 months, P=0.418). On the other hand, the treatment-related toxicity showed no statistically significant difference between these two groups (P>0.05).. The study indicated that sodium glycididazole was an effective, promising radiation-enhancing agent that improved CNS disease control rate, extended the median CNS progression-free survival time and was well tolerated in patients suffering from non-small cell lung cancer with multiple brain metastases.

Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Imidazoles; Lung Neoplasms; Male; Middle Aged; Radiation-Sensitizing Agents

Chemoresistance to cisplatin in lung cancer treatment remains prevalent. Since targeting excision repair cross-complementing 1 (ERCC1) may be a viable strategy to reestablish the therapeutic sensitivity to platinum-based agents in chemoresistant cases, and low ERCC1 level is beneficial to metastatic lung cancer patients undergoing platinum-based chemotherapy, we hypothesized that metastasis-associated process is involved in ERCC1-dependent cisplatin-resistance in lung adenocarcinoma.. We performed an RNA-Sequencing (RNA-Seq) analysis to identify differentially expressed genes in ERCC1-deficient cells co-treated with cisplatin and sodium glycididazole (CMNa). Differentially expressed genes and the hub genes in the cisplatin/CMNa-treated cells were identified by systematic network analysis. Oncomine expression analysis was also performed to evaluate the clinical implication of the identified hub gene.. Platelet-derived growth factor receptor (PDGF/PDGFR) and focal adhesion genes were downregulated in ERCC1-defective non-small cell lung cancer (NSCLC) cells undergoing combined cisplatin/CMNa treatment. Consistent with the finding, cell migration was reduced in these cells. PDGFRB was identified as the hub gene in the process by differential expressed gene network analysis. Importantly, elevated PDGFRB level was observed in advanced lung adenocarcinoma patients with metastases.. PDGF/PDGFR and focal adhesion signaling may serve as another mechanism in addition to ERCC1-mediated cisplatin-resistance in lung adenocarcinoma. Multiple pro-invasion/pro-migration/proliferation and DNA damage repair pathways may be integrated to confer growth advantages on tumor cells.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cisplatin; DNA-Binding Proteins; Drug Resistance, Neoplasm; Drug Synergism; Endonucleases; Focal Adhesions; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Imidazoles; Lung Neoplasms; Receptors, Platelet-Derived Growth Factor; RNA Interference; Sequence Analysis, RNA; Signal Transduction

Resistance to platinum-based chemotherapy becomes a major obstacle in lung cancer treatment. Compensatory activation of nucleotide excision repair (NER) pathway is the major mechanism accounting for cisplatin-resistance. We aimed at identifying additional regulators in NER-mediated chemoresistance in a hypoxic setting induced by sodium glycididazole (CMNa)-sensitized cisplatin chemotherapy of non-small cell lung cancer (NSCLC).. We performed an RNA-sequencing (RNA-Seq) analysis to identify the genes whose expression had been differentially regulated in NER-deficient cells that had been treated by cisplatin/CMNa. DNA damage, apoptosis, and correlational analysis between the differentially expressed gene and drug sensitivity were determined by Western blots, flow cytometry and Oncomine expression analysis.. The stress response gene, NDRG1 (N-Myc downstream-regulated gene 1), was among the differentially expressed genes in NER-deficient cells upon treatment of cisplatin/CMNa. Downregulation of NDRG1 by ERCC1 (excision repair cross-complementing 1) could be a prevalent mechanism for drug resistance. Furthermore, lower NDRG1 level is observed in human lung cancer cells showing chemotherapeutic drug resistance compared with the drug-sensitive cells.. NDRG1 is an important modulator linking DNA damage response and hypoxia-related cellular stress response during the development of drug resistance to cisplatin/CMNa in lung cancer. Targeting both NDRG1 and ERCC1 may be a viable strategy for overcoming drug resistance in cancer therapy, and has significant clinical implications.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Cycle Proteins; Cell Line, Tumor; Cisplatin; DNA Damage; DNA Repair; DNA-Binding Proteins; Down-Regulation; Drug Resistance, Neoplasm; Endonucleases; Humans; Imidazoles; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; RNA Interference; RNA, Small Interfering; Tumor Hypoxia