Treatment of patients with non-small cell cancer and EGFR mutations

Skřičková, Jana; Robešová, Blanka; Venclíček, Ondřej; Kadlec, Bohdan; Tomíšková, Marcela; Jakubíková, Lenka; Špeldová, Jana; Merta, Zdeněk

doi:10.36290/xon.2018.032

Cited by 4 publications

(5 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More than 80% of clinical lung cancer cases are diagnosed as non-small cell lung cancers (NSCLC) and only less than 20% as small cell lung cancer (SCLC) [1,2], but NSCLC typically grow at a slower rate than SCLC and are difficult to be discovered until they have advanced [3]. As SCLC can be diagnosed at earlier stages, chemotherapy is the major treatment for SCLC instead of surgical treatment, resulting in more drug resistance issues [4].…”

Section: Introductionmentioning

confidence: 99%

MiR-199a-5p/p62 regulated autophagy in SCLC

2022

Preprint

View full text Add to dashboard Cite

Background Autophagy has been found to be involved in the Multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC. Methods We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC. Results H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 μg/ml for 24 hours increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples. Conclusions The regulation of autophagy by the MiR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.

show abstract

Section: Introductionmentioning

confidence: 99%

MiR-199a-5p/p62 regulated autophagy in SCLC

2022

Preprint

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…NSCLC accounts for 85% of lung cancer [1]. For subtypes of lung cancer there is adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, which respectively account for 38.5%, 20%, and 3% of total lung cancer in 2018 (1). For NSCLC cancer, there are multiple therapy types available, including surgery, radiation, chemotherapy, immunotherapy, radiofrequency ablation palliative procedures, and targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Sotorasib and other drugs comparison in treating non-small cell lung cancer

Ren¹

2022

HSET

View full text Add to dashboard Cite

KRAS G12C is associated with poor diagnosis in non-small cell lung cancer (NSCLC), and this mutation accounts for 14% of total lung adenocarcinomas. Sotorasib is a KRAS G12C inhibitor drug that selectively treats NSCLC with KRAS G12C mutation. Other target therapies are available to treat NSCLC, and how Sotorasib differs in drug performance compared to other targeted therapies are not fully understood. This literature review compared Sotorasib with other NSCLC targeted therapy drugs to discuss the efficacy, side effect, and resistance between Sotorasib and other drugs that target NSCLC. Overall, Sotorasib did not show a pharmaceutical development innovation as it does not show an advantage in efficacy, side effects, and resistance compared to other drugs. Through reviews, Sotorasib could involve in group treatment with ErbB inhibition drug to better enhance the resistance outcome of the drug. As the side effect of both drugs is all severe, the safety of the combination needs further experiments.

show abstract

“…Lung cancer is the main cause of cancer-related mortality worldwide, and non-small cell cancer accounts for approximately 85% of all lung cancer cases (1,2). It is mainly characterized by a poor prognosis and a high risk of recurrence.…”

Section: Introductionmentioning

confidence: 99%

Ceramide induces the apoptosis of non‑small cell lung cancer cells through the Txnip/Trx1 complex

et al. 2021

View full text Add to dashboard Cite

ceramide is a biologically active sphingomyelin that inhibits cell growth and proliferation. In previous studies, it was demonstrated that the use of lipopolysaccharides induces acid sphingomyelinases to produce ceramide, promoting lung cancer cell apoptosis; however, the specific mechanisms of this action remain unclear. Thioredoxin-interacting protein (Txnip) plays an important role in the signal transmission of redox reactions inside and outside the cell. Thus, it was hypothesized that ceramide induces apoptosis in lung adenocarcinoma cells (A549 and Pc9) by modulating the Txnip/Trx1 complex. In the present study, the cell counting kit-8 method was used to detect cell activity and the drug concentration. Hoechst 33258 staining and flow cytometry were used to detect cell apoptosis, and the positional association between Txnip and Trx1 upregulated by ceramide was observed by immunofluorescence confocal microscopy. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the changes in related gene, mRNA and protein expression levels. The results revealed that ceramide treatment resulted in the upregulation of Txnip and in the reduction of Trx1 activities. However, the Txnip inhibitor, verapamil, reversed these changes. The analysis of mRNA expression further verified the changes observed in the protein expression of Txnip, Trx1 and apoptosis-related proteins. On the whole, the present study demonstrates that ceramide induces the apoptosis of lung cancer cells by regulating the Txnip/Trx1 complex.

show abstract

Treatment of patients with non-small cell cancer and EGFR mutations

Cited by 4 publications

References 14 publications

MiR-199a-5p/p62 regulated autophagy in SCLC

MiR-199a-5p/p62 regulated autophagy in SCLC

Sotorasib and other drugs comparison in treating non-small cell lung cancer

Ceramide induces the apoptosis of non‑small cell lung cancer cells through the Txnip/Trx1 complex

Contact Info

Product

Resources

About