Abstract Background Hepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions. Methods A two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with BCLC-C HCC who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated. Results The median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n = 66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n = 56) and PD-1 inhibitors plus targeted therapy (PT, n = 41). The median progression-free survival was 8.37 months (95% CI 6.35–10.39) with HPT versus 5.3 months (95% CI 3.48–7.12) with PTH versus 6.33 months (95% CI 3.75–8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45–0.97, p = 0.027) and PT group (HR 0.60, 95% CI 0.39–0.92, p = 0.01). The median overall survival was 14.6 months (95% CI 10.6–18.7) with HPT, 10.0 months (95% CI 8.2–11.8) with PTH and 11.3 months (95% CI 8.3–14.3) with PT. The 1-year OS rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361–0.996, p = 0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416–1.032, p = 0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients. Conclusions Initial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.
This study aimed to investigate the effect of dural puncture epidural (DPE) combined with small-dose lidocaine for labor analgesia. Parturients were randomly divided into epidural anesthesia (EA), DPE1, and DPE2 groups. In the EA group, 5 mL of 1% lidocaine was administered via conventional L2-L3 puncture catheterization; in the DPE1 group, epidural drug was administered after catheterization using the DPE technique; in the DPE2 group, epidural puncture drug was administered through the epidural puncture needle before catheterization using the DPE technique. The primary outcome was the onset time of analgesia. The secondary outcomes included the numerical rating scale (NRS) scores during uterine contraction before bolus injection of experimental dose (T0) and the second time (T1), the fifth time (T2) and the tenth time (T3) after bolus injection of experimental dose; NRS scores at the second stage of labor (T4) and during perineal suture (T5); operation time of anesthesia; puncture related complications; anesthesia related complications; delivery outcome; use of local anesthesia during vaginal suture; and Apgar score of the neonates. There were 115 women included. The onset time in the DPE2 group was markedly shorter than in the EA and DPE1 groups (P < .001). The NRS scores in the DEP2 group at T1 and T4 were significantly lower than in the EA and DEP1 groups (P < .001). The overall incidence of puncture related complications in the DEP1 and DEP2 groups was markedly higher than in the EA group (P < .05). In dural puncture epidural analgesia, when the experimental dose was injected directly through the epidural puncture needle, the onset time was shorter and the analgesic effect was better as compared to the injection of test dose after inserting the epidural catheter.
Long non-coding RNAs (lncRNAs) can serve as oncogenes and tumor suppressors and are involved in tumorigenesis and chemotherapy resistance. Brain cytoplasmic RNA 1 (BCYRN1), as a translational modulator, is an lncRNA comprised of 200 bases that plays an important role in multiple cancers. In this study, we explored the biological role of the lncRNA, BCYRN1, in the development of non-small cell lung cancer (NSCLC). We found that BCYRN1 was increased in NSCLC, and its downregulated expression could suppress NSCLC cell proliferation and cell cycle progression by inhibiting the Wnt/β-catenin pathway. Our results showed that the expression of BCYRN1 was higher in lung cancer cells compared with a normal bronchial epithelial cell line. Moreover, downregulation of BCYRN1 expression could inhibit cell proliferation and migration and induce apoptosis. Knockdown of BCYRN1 in NSCLC cells reduced a cohort of molecules (β-catenin, c-Myc and cyclin D1) which are critical for cell proliferation and apoptosis. Our results suggested that BCYRN1 induces the proliferation and migration of NSCLC cells and plays an important role in NSCLC progression. BCYRN1 may provide a new target for therapeutic intervention in NSCLC.
Several studies have demonstrated that the isolated side population (SP) cells from solid tumors exhibit cancer stem cell‑like properties, and are responsible for drug resistance during chemotherapy and tumor recurrence. In the current study, cancer stem cell‑like SP cells were isolated in the MDU‑22 breast cancer cell line using the Hoechst‑33342 dye exclusion technique. It was observed that SP cells accounted for 3.8% of cells in the MDU‑22 cell line, which was reduced to 0.6% in the presence of verapamil, an inhibitor of the ABC transporter. The sorted SP cells showed an elevated expression of stem cell markers, including ABCG2, OCT‑4 and EpCAM. Furthermore, it was demonstrated that the isolated SP cells undergo rapid proliferation and have a high survival rate. These results indicate that the coexpression of adenosine triphosphatase binding cassette transporters and stem cell surface markers in SP cells may contribute to chemoresistance, tumor recurrence, metastasis and invasion. Therefore, the isolation and characterization of SP cells may provide novel insights for the development of alternative therapeutic agents to target cancer stem cells.
Breast cancer (BC) is the most common malignant tumor among females. Although there are multiple treatments for breast cancer, many patients still face the dilemma of drug resistance after multiline treatment. It would be greatly helpful for clinical work to identify additional and improved prognostic predictors. Y-box binding protein-1 (YB-1) is a member of the cold shock protein family, and patients with overexpression of YB-1 have a worse prognosis.This study collected 48 specimens from 48 patients with breast cancer and analyzed the clinicopathological characteristics of the patients. Immunohistochemistry, immunofluorescence, cell viability analysis, tumor spheroid formation and cell morphology, cell invasion, cycle analysis, qRT-PCR, Western blot, and tumorigenicity in BALB/c nude mice were performed to verify the results.We found that patients with overexpression of YB-1 were related to lymph node metastasis and the patients' age tended to be young. Because of the short follow-up time, a survival analysis could not be performed. Based on the results of in vitro and in vivo experiments, this study indicated that breast cancer cells with overexpression of YB-1 had stronger proliferation, migration, and invasion abilities than cells with low expression of YB-1. Compared with cells with low expression of YB-1, the proliferation, migration, and invasion abilities of YB-1 overexpressed cells were not significantly affected by adriamycin.This suggested that breast cancer cells with overexpression of YB-1 were resistant to adriamycin. Therefore, YB-1 is associated with lymph node metastasis of breast cancer cell. YB-1 could be a prognostic, predictive factor and a novel therapeutic target of BC.
Hepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions.A two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated.The median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n = 66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n = 56) and PD-1 inhibitors plus targeted therapy (PT, n = 41). The median progression-free survival was 8.37 months (95% CI 6.35-10.39) with HPT versus 5.3 months (95% CI 3.48-7.12) with PTH versus 6.33 months (95% CI 3.75-8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45-0.97, p = 0.027) and PT group (HR 0.60, 95% CI 0.39-0.92, p = 0.01). The median overall survival was 14.6 months (95% CI 10.6-18.7) with HPT, 10.0 months (95% CI 8.2-11.8) with PTH and 11.3 months (95% CI 8.3-14.3) with PT. The 1-year overall survival (OS) rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361-0.996, p = 0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416-1.032, p = 0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients.Initial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.
Abstract Background: Hepatic artery intervention combined with immunotarget therapy exerts excellent disease control and prolongs survival. However, the arrangement of hepatic artery intervention and systemic therapy confuses clinical decisions. Methods: A two-center, retrospective clinical study was approved by the Institutional Ethics Committee. From December 2018 to February 2022, patients with BCLC-C HCC who received targeted therapy plus PD-1 inhibitors with or without hepatic artery intervention were included. According to the treatment mode, the patients were assigned to three groups: initial hepatic artery intervention combined with immunotarget therapy, immunotarget therapy sequential hepatic artery interventional therapy, and immunotarget therapy only. The survival, response, and adverse events were compared among the three groups. Subgroup analysis and univariate and multivariate prognostic analyses were also evaluated. Results: The median follow-up time was 18.3 months (95% CI 16.7 to 20.0 months). A total of 163 patients with BCLC-C stage HCC were assigned to three groups: initial hepatic artery intervention plus PD-1 inhibitors plus targeted therapy (HPT, n=66), PD-1 inhibitors plus targeted therapy followed by hepatic artery intervention (PTH, n=56) and PD-1 inhibitors plus targeted therapy (PT, n=41). The median progression-free survival was 8.37 months (95% CI 6.35-10.39) with HPT versus 5.3 months (95% CI 3.48-7.12) with PTH versus 6.33 months (95% CI 3.75-8.92) with PT. The progression-free survival of the HPT group was better than that of the PTH group (HR 0.66, 95% CI 0.45-0.97, p =0.027) and PT group (HR 0.60, 95% CI 0.39-0.92, p =0.01). The median overall survival was 14.6 months (95% CI 10.6-18.7) with HPT, 10.0 months (95% CI 8.2-11.8) with PTH and 11.3 months (95% CI 8.3-14.3) with PT. The 1-year OS rates in the HPT, PTH and PT groups were 50%, 33.9%, and 34.1%, respectively. Overall survival was significantly longer in the HTP group than in the PT group (HR 0.60, 95% CI 0.361-0.996, p =0.032). Compared with the PTH group, the overall survival of the HTP group had a prolonged survival trend (HR 0.66, 95% CI 0.416-1.032, p =0.059). All treatment modalities were deemed equally safe. Multivariate analysis suggested that the mode of treatment, albumin level, Child‒Pugh grade and hepatectomy history were independent prognostic factors for BCLC-C HCC patients. Conclusions: Initial hepatic artery intervention combined with immunotarget therapy gained survival benefits with tolerable side effects compared with immunotarget sequential hepatic artery intervention and immunotarget therapy alone. Multivariate analysis suggested that liver reserve function was closely correlated with prognosis.
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