RESUMO
Background: Human epidermal growth factor receptor 2 (HER2) inhibitors play a vital role in the treatment of HER2-positive breast cancer. Numerous studies have shown that traditional HER2 inhibitors and chemotherapeutics such as albumin-paclitaxel, liposomal doxorubicin, and cyclophosphamide (TAC regimen) have different degrees of cardiotoxicity. Pyrotinib is a novel small-molecule HER2 inhibitor and has no cardiotoxicity. Here, the purpose of this study was to investigate the cardiac safety of pyrotinib with TAC regimen for HER2-positive breast cancer. Methods: In this study, 22 patients with stage I-IIIA HER2-positive breast cancer were screened, enrolled, and assigned to receive either neoadjuvant or postoperative adjuvant treatment with pyrotinib (320-400 mg, once daily) combined with TAC (albumin-paclitaxel 260 mg/m2, liposomal doxorubicin 20 mg/m2, cyclophosphamide 600 mg/m2) from December 2019 to May 2021. Patients' heart function was monitored using electrocardiogram, echocardiogram, and serological indicators. ST segment and T wave change, left ventricular ejection fraction (LVEF, %), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), creatine kinase (CK), creatine kinase myoglobin band (CK-MB), together with patients' weight, white blood cells (WBC), red blood cells (RBC), platelets, plasma lipid, and glucose were recorded. Results: Before and after the 2nd, 4th, and 6th cycles of treatment, the incidence of abnormal electrocardiogram of patients enrolled in the neoadjuvant treatment group was 36.4%, 27.3%, 27.3%, and 27.3%, respectively, while in the postoperative adjuvant treatment, the incidence was 45.5%, 36.4%, 36.4%, and 36.4%, respectively. LVEF before and after treatment in the neoadjuvant chemotherapy group was 65.36%±2.25% and 65.00%±2.15% (t=1.305, P=0.221), while in the postoperative adjuvant treatment group, LVEF was 66.27%±2.69% and 65.18%±1.89% (t=1.359, P=0.204). Pyrotinib combined with a TAC regimen may have induced a decrease in RBC. No obvious abnormality was found in the level of NT-pro-BNP, CK, CK-MB, patients' weight, WBC, platelets, plasma lipid, or glucose in all enrolled patients during the entire treatment process. Conclusions: Our findings indicated that neither neoadjuvant nor postoperative adjuvant treatment using pyrotinib combined with a TAC regimen to treat patients with HER2-positive breast cancer increased cardiotoxicity. However, the treatment may have induced a decrease in RBC and further research is needed.
RESUMO
The Dunkin Hartley (DH) guinea pig is a widely used naturally occurring osteoarthritis model. The aim of this study was to provide detailed evidence of age-related changes in articular cartilage, subchondral bone mineral density, and estradiol levels. We studied the female Dunkin Hartley guinea pigs at 1, 3, 6, 9, and 12 months of age (eight animals in each group). Histological analysis were used to identify degenerative cartilage and electron microscopy was performed to further observe the ultrastructure. Estradiol expression levels in serum were assessed, and matrix metalloproteinase 3 and glycosaminoglycan expression in cartilage was performed by immunohistochemistry. Bone mineral density of the tibia subchondral bone was measured using dual X-ray absorptiometry. Histological analysis showed that the degeneration of articular cartilage grew more severe with increasing age starting at 3 months, coupled with the loss of normal cells and an increase in degenerated cells. Serum estradiol levels increased with age from 1 to 6 months and thereafter remained stable from 6 to 12 months. Matrix metalloproteinase 3 expression in cartilage increased with age, but no significant difference was found in glycosaminoglycan expression between 1- and 3-month old animals. The bone mineral density of the tibia subchondral bone increased with age before reaching a stable value at 9 months of age. Age-related articular cartilage degeneration occurred in Dunkin Hartley guinea pigs beginning at 3 months of age, while no directly positive or negative correlation between osteoarthritis progression and estradiol serum level or subchondral bone mineral density was discovered.
