RESUMO
Oprozomib, as a second-generation orally bioavailable protease inhibitor (PI), is undergoing clinical evaluation for the treatment of haematological malignancies. In relapsed refractory multiple myeloma (RRMM) patients, oprozomib has shown good efficacy as a single agent or combination therapy. In this experiment, our purpose was to validate a sensitive and rapid method for the determination of oprozomib concentration in rat plasma by ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The samples were treated with acetonitrile as the precipitant and separated by gradient elution using a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm). Using the selective reaction monitoring (SRM) method, the measurement was finished with the ion transitions of m/z 533.18 ⶠ199.01 for oprozomib and m/z 493.03 ⶠ112.03 for tepotinib (internal standard, IS), respectively. Meanwhile, acetonitrile and 0.1% formic acid aqueous solution were used as the mobile phase, and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) of the method was 1.0 ng/mL, and the linear relationship was good in the range of 1.0-100 ng/mL. In addition, the precision of four concentration levels was determined with the values of 3.1-7.3% and the accuracy was from -14.9% to 12.9%. Moreover, the recovery was determined to be from 85.1% to 96.1%, and the values of matrix effect were no more than 110.4%. The optimized UPLC-MS/MS method was also suitable for the pharmacokinetic study of rats after a single oral administration of 21 mg/kg oprozomib.
RESUMO
The purpose of this experiment to analyze the expression and clinical significance of interleukin-17 (IL-17) in lung tissue of lung cancer patients with chronic obstructive pulmonary disease (COPD). For this aim, 68 patients with lung cancer and chronic obstructive pulmonary disease who were admitted to our hospital from February 2020 to February 2022 were selected as the research objects of the study group. The specimens were fresh lung tissue obtained after lobectomy; In addition, 54 healthy subjects were selected as the control group during the same period, and fresh lung tissue obtained by minimally invasive lung volume reduction was selected as the sample. The clinical baseline data of the two groups were observed and compared. The mean alveolar area, small airway inflammation score and Ma tube wall thickness were measured. The expression of IL-17 was detected by immunohistochemistry. Results showed that gender, average age and average body mass index of the two groups (P > 0.05); At present, the proportion of smokers, pulmonary artery systolic pressure, PaCO2 level and CRP level in the study group are high, PaO2 level, FEV1% predicted value, FEV1 / FVC and FIB level are low, and the number of acute exacerbations in the past year is high (P > 0.05). In the study group, the average alveolar area, the thickness of the Ma tube wall, the lymphocyte infiltration score of the tracheal wall and the total pathological score of the small airway were higher (P > 0.05). The expression of IL-17 in the airway wall and lung parenchyma was higher in the study group (P > 0.05). IL-17 expression in lung tissue of lung cancer patients with COPD was positively correlated with body mass index, and negatively correlated with CRP, FIB, FEV1% predicted value and the number of acute exacerbations in the past year; CRP and the number of acute exacerbations in the past year were independent variables and independent influencing factors of IL-17 expression (P < 0.05). In conclusion, IL-17 is highly expressed in the lung tissues of patients with lung cancer and COPD, which may play an important role in the occurrence and development of the disease.