ABCG2 C421A polymorphisms affect exposure of the epidermal growth factor receptor inhibitor gefitinib.

ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.

Mesenchymal-epithelial transition factor exon 14 skipping mutation-positive granulocyte colony-stimulating factor-producing lung adenocarcinoma mimicking lung abscess: A case report.

Granulocyte colony-stimulating factor (G-CSF)-producing lung tumours are rare, with their imaging features and effective treatments remaining elusive. Similarly, mesenchymal-epithelial transition (MET) exon 14 skipping mutations are also uncommon. Herein, we report a case of G-CSF-producing lung adenocarcinoma positive for a MET exon 14 skipping mutation, mimicking lung abscess. A 61-year-old man presented with cough and high fever. Contrast-enhanced chest computed tomography revealed a mass with a cavity and internal fluid accumulation. The patient initially underwent diagnostic treatment for a lung abscess but was ultimately diagnosed with lung adenocarcinoma positive for a MET exon 14 skipping mutation. Following tepotinib therapy, the primary lesion shrank, and serum G-CSF levels decreased, leading to a diagnosis of G-CSF-producing lung cancer. G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer.

Unusual Manifestation of Dermatomyositis: Exacerbation of Hypertriglyceridemia.

Systemic lupus erythematosus is known to cause autoimmune hyperlipidemia. We present a case in which hypertriglyceridemia was exacerbated by dermatomyositis. A 53-year-old woman with a medical history of undertreated hypertriglyceridemia complained of dyspnea and arthralgia. Despite the treatment, her triglyceride levels increased concurrently with the onset of arthralgia. She had characteristic skin manifestations and tested positive for anti-Jo-1 autoantibodies, leading to a diagnosis of dermatomyositis. Chronic inflammation may result in elevated triglyceride levels. When dermatomyositis is diagnosed, evaluating lipid abnormalities is important.