ABSTRACT
Purpose: Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As2O3) showed antitumor effects on HCC, the purpose of this study was to determine whether As2O3 and Nrf2-siRNA could inhibit HCC synergistically. Methods: We generated two separate 5-FU-resistant HCC cell lines (SNU-387/5-FU and Hep3B/5-FU). Western blotting was used to determine protein levels. An efficient lentiviral delivery system was used to establish stable knockdown or overexpression of Nrf2 and HIF-1α. In vitro and in vivo analyses of the effects of Nrf2 gene knockdown and As2O3 on 5-FU-resistant HCC cells were conducted. Results: The expression of Nrf2 was higher in the 5-FU-resistant HCC cell lines than in the parental cell lines. When coupled with Nrf2 knockdown, As2O3 treatment significantly decreased 5-FU-resistant SNU-387 and Hep3B cell viability, migration, and invasion, inactivated HIF-1α/HSP70 signaling, inhibited anti-apoptotic B-cell lymphoma (Bcl-2) activity, and increased the expression of pro-apoptotic Bcl-2-associated X protein (BAX) along with caspase-3. The synergistic effect was also confirmed using a 5-FU-resistant Hep3B mouse xenograft model in vivo. Conclusion: Nrf2 knockdown could improve the effect of As2O3 on reversing drug resistance in 5-FU-resistant HCC cells.
ABSTRACT
Background: To evaluate the efficacy of double percutaneous nephrostomy (PCN) combined with ureter occlusion stent for treating cervical cancer complicated with vesicovaginal fistula (VVF). Materials and Methods: A retrospective analysis was performed for 12 patients with cervical cancer complicated with VVF. Regardless of surgical resection, radiotherapy alone or combined chemoradiotherapy were carried out in all patients. After VVF was diagnosed by gynecological examination, imaging, and cystoscopy, concurrent double PCN and ureter occlusion stent implantation were performed for all patients. Results: All patients successfully received ureter occlusion stent implantation after nephrostomy. The success rate of nephrostomy and stent placement was 100% (12/12). After intervention, urinary fistula immediately disappeared in all patients. One week post-surgery, bilateral hydronephrosis disappeared in 4 patients, and their renal insufficiency and renal function returned to normal. One month after operation, 6 patients with genital eczema or ulcer and 5 patients with urinary tract infection were cured. During follow-up, there were no recurrence in urinary fistula, renal dysfunction, and other complications. Conclusion: Double PCN combined with ureter occlusion stent could effectively treat cervical cancer complicated with VVF hydronephrosis, urinary tract infection, and renal insufficiency and contribute to alleviate all kinds of clinical discomfort.
