The morbidity and mortality rates associated with non-small-cell lung carcinoma (NSCLC) are increasing every year, placing new demands on existing therapies and drugs. Ammonium ferric citrate (AFC) is often used as a food additive for iron supplementation; however, to our knowledge, no studies have investigated whether AFC can induce ferroptosis in NSCLC. In this study, we demonstrated that specific concentrations of AFC effectively inhibit the proliferation and invasion of lung cancer cell lines in vitro using a cell proliferation inhibition test, a transwell assay, and flow cytometry analysis of cell cycle and apoptosis. In addition, AFC significantly induced oxidative stress injury in lung cancer cell lines. A quantitative polymerase chain reaction assay showed that AFC markedly reduced the expression levels of cell growth factors, negative regulators of ferroptosis, and autophagy regulators. Lastly, a protein-protein interaction analysis revealed that glutathione peroxidase 4 (GPX4) exerted its biological role through the regulation of the GSS/GSR complex and downstream GGT family proteins. When the expression of GPX4 changes, its biological activities, such as the glutathione metabolic process, cellular biosynthetic process, cellular response to chemical stimulus, and antioxidant activity, change accordingly, thereby affecting the survival quality and physiological and biochemical activities of cells. Overall, this study verifies that AFC has the biological activity of activating oxidative stress injury in NSCLC cell lines, leading to a decrease in their autophagy and inducing ferroptosis. We also confirmed that the GPX4-GSS/GSR-GGT axis is a crucial target of AFC-induced ferroptosis.

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with high incidence and poor prognosis. Common treatment methods include surgery, transcatheter arterial chemoembolization (TACE), ablation, and targeted therapy. In recent years, combination treatment with antiangiogenic therapy and immune checkpoint inhibitors has made great progress in the treatment of advanced HCC. Here, we report the case of a patient with HCC who achieved a durable benefit from anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation.Main BodyA 38-year-old male patient initially presented with severe abdominal pain that was identified as an HCC rupture and hemorrhage by computed tomography (CT). The patient underwent emergency surgery and postoperative pathology confirmed HCC. The patient received prophylactic TACE after surgery. Unfortunately, three months after surgery, the patient developed multiple liver metastases. Subsequently, he received systemic anti-vascular therapy and immune checkpoint inhibitors combined with intratumoral cryoablation. After treatment, the patient achieved extensive tumor necrosis and the disease was effectively controlled.ConclusionsAnti-angiogenic therapy and immune checkpoint inhibitors combined with cryoablation can induce a powerful and effective systemic anti-tumor immune response, which is worthy of further research.

Background HER2-positive patients with advanced gastric cancer have a poor prognosis, and trastuzumab-resistant patients lack effective treatment. Case Presentation We report a 72-year-old male with HER2-positive gastric cancer. The patient had metastatic tumor during adjuvant chemotherapy after surgery, followed by second-line chemotherapy, and achieved a progression-free survival (PFS) of 4.5 months. Subsequent third-line chemotherapy treatment also failed. Fortunately, the patient had a significant tumor response and 8.5 months of PFS on trastuzumab combined with chemotherapy. After trastuzumab resistance, the patient was treated with programmed cell death protein-1 inhibitor combined with apatinib, which selectively inhibited VEGFR2, but the effect was not satisfactory. Finally, the patient was treated with capecitabine combined with pyrotinib, an irreversible TKI, acting on HER2. The tumor shrank significantly after this treatment. Conclusion The mechanism and countermeasures of trastuzumab resistance were discussed in this case. For patients with HER2-positive advanced gastric cancer, pyrotinib can achieve good results after trastuzumab resistance.

Background: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in lung. In this study, we aimed to explore the role and underlying mechanism of circular RNA 0018534 (circ_0018534) in NSCLC progression.Methods: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of circ_0018534, microRNA-153-3p (miR-153-3p) and BTB/POZ domain-containing protein 7 (BTBD7) in NSCLC tissues and cells. Protein expression was measured by western blot analysis. The morphological features of obtained NSCLC patient tissues were observed by haematoxylin and eosin staining assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, and transwell migration and invasion assays were used to examine cell viability, proliferation, apoptosis, migration and invasion, respectively. Bioinformatics analysis and dual-luciferase reporter assay were carried out to determine the interaction among circ_0018534, miR-153-3p and BTBD7. Furthermore, lentivector for short hairpin RNA against circ_0018534 (sh-circ_0018534) was used to decrease circ_0018534 expression in an animal tumor model.Results: Circ_0018534 and BTBD7 expression were significantly increased, whereas miR-153-3p expression was decreased in NSCLC tissues and cells. Circ_0018534 downregulation markedly alleviated cell proliferation, migration, invasion, and elevated cell apoptosis in NSCLC cells in vitro. MiR-153-3p inhibitors partially reversed the effects of circ_0018534 knockdown on cell proliferation, migration, invasion and apoptosis in NSCLC. Moreover, miR-153-3p could directly target BTBD7, and circ_0018534 promoted BTBD7 expression by targeting miR-153-3p. Besides, BTBD7 overexpression attenuated miR-153-3p mimics-mediated effects on NSCLC cell progression. Furthermore, circ_0018534 deletion suppressed NSCLC tumor growth in vivo.Conclusion: Our results demonstrated that circ_0018534 might contribute to the progression of NSCLC by miR-153-3p/BTBD7 axis, providing a potential target for the treatment of NSCLC.