Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small cell lung cancer (SCLC) has been a devastating actuality in clinic and the molecular mechanisms underlying this disease remain unclear. The epigenetic alterations located in the promoter region of human telomerase reverse transcriptase (hTERT) have been demonstrated as one of the most prevalent non-coding genomic modifications in multiple cancers. However, alteration of hTERT promoter methylation in SCLC and the subsequently induced change in tumor cell behavior remains unclear. In this research, we hypothesized that abnormal methylation of hTERT promotor enhanced the progression of SCLC and the outcome of radiotherapy resistance. Quantitative real-time PCR and western blot assays were performed to evaluate the RNA and protein levels of hTERT and enhancer of zeste homolog 2 (EZH2), respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to estimate the viability and X-ray sensitivity of H20 and H446 cell lines. Functionally, upregulation of hTERT promoted the proliferation and migration of H20 and H446 cells, and the high-level of methylation in the promoter region of hTERT induced by radiation caused radio-resistance in SCLC. Mechanically, methylation of hTERT promoter enhanced the progression and radio-resistance of SCLC through upregulating the expression of its downstream effector EZH2.
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PMID:hTERT promoter methylation promotes small cell lung cancer progression and radiotherapy resistance. 3276 Oct 59

Pentabromobenzylisothioureas are antitumor agents with diverse properties, including the inhibition of MAPK15, IGF1R and PKD1 kinases. Their dysregulation has been implicated in the pathogenesis of several cancers, including bronchopulmonary neuroendocrine neoplasms (BP-NEN). The present study assesses the antitumor potential of ZKKs, a series of pentabromobenzylisothioureas, on the growth of the lung carcinoid H727 cell line. It also evaluates the expression of MAPK15, IGF1R and PKD1 kinases in different BP-NENs. The viability of the H727 cell line was assessed by colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and its proliferation by BrdU (5-bromo-2'-deoxyuridine) assay. Tissue kinase expression was measured using TaqMan-based RT-PCR and immunohistochemistry. ZKKs (10-4 to 10-5 M) strongly inhibited H727 cell viability and proliferation and their antineoplastic effects correlated with their concentrations (p < 0.001). IGF1R and MAPK15 were expressed at high levels in all subtypes of BP-NENs. In addition, the SCLC (small cell lung carcinoma) patients demonstrated higher mRNA levels of IGF1R (p = 0.010) and MAPK15 (p = 0.040) than the other BP-NEN groups. BP-NENs were characterized by low PKD1 expression, and lung neuroendocrine cancers demonstrated lower PKD1 mRNA levels than carcinoids (p = 0.003). ZKKs may suppress BP-NEN growth by inhibiting protein kinase activity. Our results suggest also a possible link between high IGF1R and MAPK15 expression and the aggressive phenotype of BP-NEN tumors.
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PMID:IGF1R and MAPK15 Emerge as Potential Targets of Pentabromobenzylisothioureas in Lung Neuroendocrine Neoplasms. 3313 24


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