RESUMEN
BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as neoadjuvant chemotherapy (NAC) for breast cancer remains controversial. We conducted a retrospective study to compare the efficacy and safety of nab-paclitaxel with those of docetaxel as neoadjuvant regimens for HER2-negative breast cancer. METHODS: In this retrospective analysis, a total of 159 HER2-negative breast cancer patients who had undergone operation after NAC were consecutively analyzed from May 2016 to April 2018. Patients were classified into the nab-paclitaxel group (n = 79, nab-paclitaxel 260 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) and the docetaxel group (n = 80, docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) according to the drug they received for neoadjuvant treatment. The efficacy and adverse events were evaluated in the two groups. RESULTS: The pathological complete response (pCR)(ypT0/isN0) rate was significantly higher in the nab-paclitaxel group than in the docetaxel group (36.71% vs 20.00%; P = 0.031). The multivariate analysis revealed that therapeutic drugs, lymph node status, and tumor subtype were the most significant factor influencing treatment outcome. At a median follow-up of 47 months, disease-free survival (DFS) was not significantly different in those assigned to nab-paclitaxel compared with docetaxel (82.28% vs 76.25%; P = 0.331). The incidence of peripheral sensory neuropathy in the nab-paclitaxel group was higher than that in the docetaxel group (60.76% vs 36.25%; P = 0.008), while the incidence of arthralgia was observed more frequently in the docetaxel group (57.50% vs 39.97%; P = 0.047). CONCLUSIONS: Compared with docetaxel, nab-paclitaxel achieved a higher pCR rate, especially those patients with triple-negative breast cancer or lymph node negative breast cancer. However, there was no significant difference in DFS between the two groups. This study provides a valuable reference for the management of patients with HER2-negative breast cancer.
RESUMEN
Forkhead box protein O1 (FOXO1) is a multifunctional transcription factor of the forkhead family. It may function as a tumor suppressor through its ability to regulate cellular events, including cell proliferation, apoptosis, and cell cycle control. As reported, FOXO1 is downregulated in papillary thyroid carcinoma (PTC). However, the function of FOXO1 in human PTC remains unclear. In this study, we investigated the function and underlying regulatory mechanisms of FOXO1 in PTC cells. PTC cell lines K1 and TPC1 were transiently transfected with FOXO1 small interfering RNA (siRNA) and negative control RNA. Successful transfection was confirmed by RT-qPCR and Western blot analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays, colony formation assays, apoptosis, and cell cycle assays were used to explore the potential function of FOXO1 in the PTC cell lines. We found that downregulation of FOXO1 promoted cellular proliferation, enhanced clonogenesis, and inhibited cellular apoptosis. However, the cell cycle was not markedly affected by FOXO1 siRNA. Furthermore, Bim, a downstream target of the Akt/FOXO1 signaling pathway, was downregulated at both mRNA and protein levels in cells transfected with FOXO1 siRNA. Collectively, these results indicate that FOXO1 may play an important role in inhibiting PTC development by regulating cellular proliferation, growth, and apoptosis. FOXO1 expression is a potentially useful biomarker for human PTC. Moreover, tumorigenesis of PTC may be associated with repression of the Akt/FOXO1/Bim signaling pathway.
RESUMEN
MicroRNAs (miRNAs) are kind of small non-coding RNAs that negatively regulate gene expression at post-transcription level, and those non-coding RNAs appear to play a key role in tumorigenesis. The aim of this study was to investigate the biological role of miR-96 in papillary thyroid carcinoma (PTC) cell lines. We identified miR-96 to be up-regulated in PTC specimens in comparison to matched normal tissues by microRNA microarray and RT-qPCR analysis (P < 0.05). Next, to explore the potential function of miR-96, PTC cell lines K1 and TPC1 were transiently transfected with miR-96 mimics and inhibitor. Successful transfection being confirmed by RT-qPCR. Ectopic expression of miR-96 promoted proliferation and colony formation ability, and inhibited apoptosis of K1 and TPC1 cells, whereas down-regulated expression of miR-96 suppressed those functions when compared with the control cells. According to a computational prediction, FOXO1 maybe a potential target of miR-96. Luciferase assays revealed that miR-96 is directly targeted to both binding sites of FOXO1 3'-untranslated region (3'-UTR) and suppressed the FOXO1 expression, and subsequently inhibited the expression of Bim protein in PTC cells. Moreover, the expression of FOXO1 had an inverse correlation with expression of miR-96 in PTC specimens by RT-qPCR and western blot analysis. The data from the present study demonstrated that miR-96 can promote proliferation, and inhibit apoptosis in PTC cell lines K1 and TPC1, thus miR-96 may play an oncogenic role in PTC by inhibiting the FOXO1 and regulating AKT/FOXO1/Bim pathway, and it may serve as a novel therapeutic target for miRNA-based PTC therapy.