RESUMEN
A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.
RESUMEN
Deregulation of the microRNAs (miRNAs), a cluster of important posttranscriptional regulators, has been frequently associated with lung cancer (LCa). However, the emerging mechanism for how miRNAs is linked causally in the development of LCa chemoresistance is poorly understood. Herein, we established for the time the up-regulation of miR-369-3p in cisplatin (DDP)-resistant nonsmall cell lung cancer (NSCLC) tissues and cells. Its deregulation was found to be correlated to the magnitude of malignancy in well-characterized LCa cells. Functionally, inhibition of miR-369-3p sensitized LCa cells to DDP and suppressed the invasive capability in the presence of DDP treatment, whereas miR-369-3p overexpression promoted DDP resistance and thereby enhanced LCa cells invasiveness. Mechanistically, bioinformatics coupled with luciferase and gain-of-function, loss-of-function assays revealed that miR-369-3p may regulate DDP chemoresistance by directly targeting the 3' untranslated region (UTR) of human solute carrier 35F5 (SLC35F5), as application of miR-369-3p inhibitors or reintroduction of epigenetically silenced SLC35F5 both individually sensitized LCa cells to DDP, but combined treatment with miR-369-3p inhibitors and SLC35F5 overexpression failed to sensitized LCa cells further to DDP-elicited cell death. Our results provide evidence that the oncomiR effect of miR-369-3p may be mediated through disrupting the nucleotide sugar transportation and that SLC35F5 is a key effector of this chemoresistance-promoting activity.
