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BACKGROUND: In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. MAIN BODY: Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. CONCLUSION: ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach.
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Background: Identification of the intersegmental plane (ISP) is the critical step in lung segmentectomy because of the complicated anatomic variations. Bronchial methylene blue staining was developed by our team in 2015 and is now commonly used at our center, it could rapidly and accurately identify the ISP. In this study, we aimed to compare bronchial methylene blue staining with the modified inflation-deflation method in terms of their perioperative characteristics and to present our experience of the methylene blue method. Methods: From June 2020 to September 2021, the data of 112 patients with pulmonary ground-glass nodules who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Sixty-two patients underwent bronchial methylene blue staining, and 50 patients underwent the modified inflation-deflation method. Results: Both methods could accurately identify the ISP. The time taken to clearly display the ISP (82.94±28.08 vs. 868.20±145.89 seconds; P<0.001) and the surgical duration (131.69±32.05 vs. 146.08±28.11 minutes; P=0.014) were significantly shorter in the bronchial methylene blue staining group than in the modified inflation-deflation group. There were no significant differences between the two groups in the bleeding volume, drainage time, and length of postoperative hospital stay, as well as in most other perioperative characteristics. Conclusions: Compared with the modified inflation-deflation method, the bronchial methylene blue staining method can quickly display the ISP and shorten the surgical duration. This method is safe and feasible, can be widely applied during thoracoscopic anatomic segmentectomy.
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OBJECTIVE: To investigate the expression of protein kinase B (PKB) in human-squamous cell carcinoma (SCC) and adenocarcinoma of lung (ADC) and in benign lung tissues (BD, lung tissues adjacent to cancer or from patients with benign lung diseases), and its association to clinicopathological characteristics. METHODS: The PKB expression in 41 specimens from patients with SCC (26 cases) and ADC (15 cases) and in 12 specimens from patients with benign lung diseases (BD) were investigated by immunohistochemistry and Western blot analysis. RESULTS: PKB in benign lung tissues was usually weakly stained and scattered in distribution. It was remarkably increased in lung cancer compared to benign lung tissue. The positive rates of PKB in SCC and ADC were 50% (13/26), 60% (9/15), respectively, and there was no significant difference between them. PKB expression was significantly stronger in lung cancer patients in advanced stages (stage III or IV) or with poor differentiation, than those in early stages (stage I or II) or with moderate or well differentiation. The expression was stronger in patients with local lymph node metastasis than those without (P = 0.0391). CONCLUSION: PKB protein is over-expressed in human squamous-cell carcinoma and adenocarcinoma of lung.