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Author(s):  
Di Che ◽  
Mingshuo Wang ◽  
Juan Sun ◽  
Bo Li ◽  
Tao Xu ◽  
...  

Keratin 6A (KRT6A) belongs to the keratin protein family which is a critical component of cytoskeleton in mammalian cells. Although KRT6A upregulation in non-small cell lung cancer (NSCLC) has been reported, the regulatory mechanism and functional role of KRT6A in NSCLC development have been less well investigated. In this study, KRT6A was confirmed to be highly expressed in NSCLC tissue samples, and its high expression correlated with poor patient prognosis. Furthermore, overexpression of KRT6A promotes NSCLC cell proliferation and invasion. Mechanistically, KRT6A overexpression is sufficient to upregulate glucose-6-phosphate dehydrogenase (G6PD) levels and increase the pentose phosphate pathway flux, an essential metabolic pathway to support cancer cell growth and invasion. In addition, we discovered that lysine-specific demethylase 1A (LSD1) functions upstream to promote KRT6A gene expression. We also found that the MYC family members c-MYC/MYCN are involved in KRT6A-induced G6PD upregulation. Therefore, this study reveals an underappreciated mechanism that KRT6A acts downstream of LSD1 and functions as a pivotal driver for NSCLC progression by upregulating G6PD through the MYC signaling pathway. Together, KRT6A and LSD1 may serve as potential prognostic indictors and therapeutic targets for NSCLC.


2021 ◽  
Author(s):  
Wenjie Sun ◽  
Shuying Li ◽  
Guiliang Tang ◽  
Shaoxing Sun ◽  
Yuan Luo ◽  
...  

2021 ◽  
Author(s):  
Changlong He ◽  
Chengcheng Wei ◽  
Jun Wen ◽  
Shi Chen ◽  
Ling Chen ◽  
...  

Abstract BackgroundBy comparing the detection rate and type of targeted gene mutations in non-small cell lung cancer (NSCLC) between amplification refractory mutation system PCR (ARMS-PCR) and next generation sequencing (NGS), the characteristics and application advantages of non-small cell lung cancer detection are explained, providing a basis for clinicians to effectively select the corresponding detection methods.Methods and materials The cases of targeted genes for lung cancer were selected from the First Affiliated Hospital of Chongqing Medical University from January 2016 to October 2020. A sample of 4467 cases was selected,and they were diagnosed with NSCLC by Pathological biopsy. Sample sources include surgical resection, bronchoscope biopsy, metastatic biopsy, blood, sputum, cytology of pleural effusion. Among them, 3665 cases were detected by ARMS-PCR technique, and 802 cases were detected by NGS technology. The detection rate and type of ARMS-PCR and NGS techniques for EGFR gene mutations (including exon 18, exon 19, exon 20, exon 21 and so on) in different NSCLC samples were compared respectively.ResultsThe total mutation rate of EGFR gene detected by ARMS-PCR was 47.6% while 42.4% detected by NGS which indicated that there was a significant difference between the two methods in detecting total mutation of EGFR gene (P<0.001). In different exons, the EGFR mutation rate detected by two methods is various. The mutation rate of exon 19 by ARMS-PCR detection was evidently higher than that of NGS detection, while the mutation rate of exon 20 and 21 by ARMS-PCR detection were statistically significantly lower than that of NGS detection. Moreover, the multiple mutation rate detected by NGS was 16.3% which was much higher than the 2.7% detected by ARMS-PCR with statistically different. ConclusionsIt showed that NGS could direct the drug use for the resistant patients. However, some rare loci could be detected by NGS but the importance and directed meaning are still unknown and the number of rare mutations is rare too. Further research on new biomarkers and technique is still needed for early diagnosis, directing drug use and assessing the therapy prognosis.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 912
Author(s):  
Marion FERREIRA ◽  
Thomas SECHER ◽  
Nathalie HEUZE-VOURC’H ◽  
Karen L RECKAMP

Several types of antibodies (Abs) are currently used in non-small cell lung cancer (NSCLC). Anti-angiogenic and immune checkpoint inhibitor (ICI) Abs are the most frequent treatments used alone or with chemotherapy in metastatic NSCLC, for the front line and beyond. Considering the many therapeutic options for locally advanced and metastatic lung cancer and differences in use according to geographic area, we present here a comprehensive review of the marketed ICI and anti-angiogenic Abs approved in the European Union (EU) and the US to treat locally advanced and metastatic NSCLC patients. We briefly describe the different molecules and their development in thoracic oncology and compare pharmacokinetic data, processing decision algorithms and marketing authorizations by the EMA and US Food and Drug Administration (FDA).


2021 ◽  
Vol 2 (2) ◽  
pp. 42-49
Author(s):  
S. N. Tikhonova ◽  
D. A. Rozenko ◽  
N. D. Ushakova ◽  
N. N. Popova ◽  
A. M. Skopintsev ◽  
...  

The article describes a clinical case of surgical treatment of a patient with multiple primary malignant lesions of the lungs (cancer of the left lung, central peribronchial nodular tumor with involvement of the upper lobe and distal parts of the main bronchus; cancer of the right lung, central tumor with involvement of the upper lobar bronchus). Radical treatment became possible due to using the potential of artifi cial gas exchange of both lungs with two devices with fundamentally different ventilation mechanics. The choice of an optimal tactics for the functional correction of the supposed hypoxemia by volumetric and high-frequency pulmonary ventilation allowed avoiding an imbalance in the ventilation/perfusion ratio and preventing the development of life-threatening complications, as well as ensured an adequate gas exchange for the patient during surgical treatment.


2021 ◽  
Author(s):  
Peiliang Wang ◽  
Tianwen Yin ◽  
Kaikai Zhao ◽  
Jinming Yu ◽  
Feifei Teng

Abstract Purpose: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aim to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods: We retrospectively identified oligometastatic NSCLC (≤4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS) . Results: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of radiotherapy to ICI therapy significant increased the best ORR from 31.2% to 50.8%, p=0.015). The out-of-field (abscopal`) response rate could reach 41.3% (95% CI, 26.5%-56.1%) in the ICI plus RT group. Median progression-free survival was 8.9 months (95%CI, 4.7-13.1 months) with ICI alone versus 13.8 months (95% CI, 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.568; p=0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients with aged <65 years (p=0.016), patients with ECOG PS=0 (p=0.048), patients with 1-2 metastatic sites (p=0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm.Conclusion: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.


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