The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells ...(HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.
Lenvatinib (LENV) and atezolizumab/bevacizumab (ATE/BEV) have been approved as first-line regimens for the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to compare their clinical ...efficacy and safety. Patients receiving ATE/BEV (n = 86) or LENV (n = 146) as first-line treatment were recruited from three academic hospitals in Korea. Overall survival (OS), progression-free survival (PFS), and radiological response were assessed according to the Response Evaluation Criteria in Solid Tumors. Clinical features of the two groups were balanced through propensity score (PS) matching with a 1:1 ratio and inverse probability of treatment weighting (IPTW) analyses. The median age was 62 years, with male predominance (83.6%). There was no significant difference in the objective response rate between the ATE/BEV and LENV groups (32.6% vs. 31.5%; p = 0.868). Neither median OS (not reached vs. 12.8 months; p = 0.357) nor PFS (5.7 vs. 6.0 months; p = 0.738) was different between ATE/BEV and LENV groups. PS-matched and IPTW analyses yielded comparable results in terms of OS and PFS (all p > 0.05). Grade ≥ 3 adverse events occurred in 42.8% and 21.9% of patients in the ATE/BEV and LENV groups, respectively (p = 0.141). The two first-line therapy regimens for unresectable HCC had comparable clinical efficacy and safety in real-world practice settings. Further studies with a larger sample size and longer follow-up are needed to validate these results.
Purpose
To investigate whether the use of an activity tracker with feedback increases physical activity and is safe in patients who underwent a midline laparotomy for gynecologic disorders.
Methods
...Patients who were planned to undergo a midline laparotomy for gynecologic diseases wore an activity tracker at baseline and from postoperative days 1–6. Patients in the experimental arm could monitor their step counts and were encouraged to achieve the individualized step‐count goal daily. In contrast, patients in the control arm did not monitor their step‐counts and received the usual encouragement for ambulation. The primary endpoint was the percentage of the average step‐count at postoperative days 4–5 divided by the baseline activity count.
Results
Seventy‐three patients were randomized; 63 patients underwent a surgery and wore an activity tracker; 53 patients were evaluable for primary endpoint. The activity recovery rate was significantly higher in the experimental arm compared to the control arm (71% vs 41%, p < 0.01). However, the study arm was not significantly associated with the activity recovery rate in multivariate analysis. The brief pain inventory score, brief fatigue inventory score, day of first flatus, day of soft blend diet initiation, ileus incidence, and length of postoperative hospital stay were similar between arms. The incidence of wound dehiscence and other adverse events were similar between arms. There were no grade 3 of 4 adverse events.
Conclusion
The use of an activity tracker with feedback is safe and may increase physical activity in patients who have undergone major gynecologic surgery.
To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with ...rheumatoid arthritis (RA).
This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100.
A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively).
Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101.
ClinicalTrials.gov, NCT02715908 . Registered 22 March 2016.
Highlights•The titer of a PR8-derived clade 2·3·4·4a H5N8 virus in chicken embryo was very low. •H103Y mutation in HA increased virus titer in chicken embryo and thermo-stability. •H103Y mutation ...increased mammalian pathogenicity of the virus as reported. •Replacement of PR8 and a prototypic PB2 genes removed the pathogenicity. •The safe and productive virus protected chickens from fatal H5N6 virus challenge.
This paper examines the political and cultural context of the popular 2010 revival of the light comedy theatre production Sanullim in North Korea. The play, originally written and performed in 1961, ...portrays the spirit of revolutionary optimism as the characters resolve an unhostile conflict and unite to expand socialist production to contribute to overcoming the (real-life) political and economic crisis of the Chollima era. The 2010 revival of this propaganda responded to similar political and economic crisis, and was designed to instil confidence that the present crisis would be overcome as successfully as in the first Chollima era, provided that people could conjure the same revolutionary optimism. This paper examines why this particular play was revived over others from the Kim Il-sung era, and its particular potential to serve as effective propaganda during the transition from military-first to party-first policy in the Kim Jong-un era, in reference to parallels between 1961 and 2010. The play immerses the audience in the dramatic situations through verisimilitude to the lives of the audience, though the emotional excess of the characters is often exaggerated. Such laughter ignited by dramatic irony contributed to creating a heightened ideological thought of the audience who would spontaneously (re-)internalise the communist human character. The revival of the play was the most appropriate choice according to the object of justification of the succession of power from Kim Jung-il to Kim Jung-un.
•Consumer perception of healing foods was explored through Q-methodology and sorting.•Three distinct consumer groups emerged based on their perspectives.•Group 1 emphasized the importance of healing ...foods for physical health benefits.•Group 2 prioritized emotional benefits in their definition of healing foods.•Group 3 linked healing foods to seasonal ingredients and eco-friendly preparation.
With the global surge in interest in healing following the COVID-19 pandemic, there has been a growing interest in the concept of healing within the context of food. However, a clear understanding of how consumers perceive and define healing food is lacking. This study aimed to investigate consumer perceptions of healing food and the underlying elements that constitute the concept. Eighty subjects, evenly distributed across genders and age groups (19 to 65), conducted Q sort of 35 statements related to healing foods. Additionally, they sorted 46 food items into categories according to whether they considered them healing foods. The subjects were categorized based on their perceptions of healing foods. Group 1 emphasized physical health benefits of healing foods, identifying dairy, nuts, and functional beverages as healing foods. Group 2 valued the emotional benefits, choosing foods for sensory pleasure to alleviate negative emotions. Group 3 prioritized seasonal ingredients and eco-friendly preparation methods, with an older average age compared to the other groups. The results revealed a multidimensional nature of healing food, encompassing both physical and mental aspects. Interestingly, different consumer groups placed emphasis on distinct facets of healing foods and selected different items as representative of such foods. These findings highlight the nuanced nature of the healing concept and provide a valuable insight for deeper investigations into strategies for understanding and promoting healing foods.
Objectives
The objective is to evaluate the prognostic value of serum human epididymis protein 4 (HE4) as a tumor marker in patients with cervical cancer.
Methods
Sixty-seven patients with cervical ...cancer treated at Seoul National University Bundang Hospital from September 2014 to May 2018 were retrospectively reviewed. Serum HE4 levels were measured by immunoassay before starting primary treatment. A mean serum HE4 level of 72.6 pmol/L was used to divide the patients into low and high HE4 groups. Patient characteristics, clinicopathological variables, and survival outcomes were compared between the two groups.
Results
The low and high HE4 groups included 55 (82.1%) and 12 (17.9%) patients at diagnosis, respectively. Higher HE4 levels were significantly associated with older age at diagnosis (age <50: .0% vs age ≥50: 100.0%; P = .002), menopause (premenopause: 8.3% vs postmenopause: 91.7%; P = .009), higher FIGO stage (stage I–II: 33.3% vs III–IV: 66.7%; P = .017), large tumor size (<4.0 cm: 41.7% vs ≥4.0 cm: 58.3%; P = .029), positive lymph node metastasis (negative: 41.7% vs positive: 58.3%; P = .049), and involvement of the parametrium (negative: 25.0% vs positive: 75.0%; P = .002). Higher HE4 level was a predictive factor for worse overall survival but not for progression-free survival. Elevated HE4 levels were not independent factors for the prediction of either overall survival or progression-free survival. Subgroup analysis by histological type revealed similar results for patients with squamous cell carcinoma.
Conclusions
High levels of HE4 expression correlated with poor overall survival, indicating that elevated HE4 levels are associated with a poor prognosis for patients with cervical cancer.
A series of one-dimensional column experiments was conducted to examine the effects of tube length on the transport and deposition of 4-ethoxybenzoic acid functionalized multi-wall carbon nanotubes ...(MWCNTs) in water-saturated porous media. Aqueous MWCNTs suspensions were prepared to yield three distributions of tube lengths; 0.02–1.3 μm (short), 0.2–7.5 μm (medium), and 0.2–21.4 μm (long). Results of the column studies showed that MWCNT retention increased with increasing tube length. Nevertheless, more than 76% of the MWCNT mass delivered to the columns was detected in effluent samples under all experimental conditions, indicating that the functionalized MWCNTs were readily transported through 40–50 mesh Ottawa sand. Examination of MWCNT length distributions in the effluent samples revealed that nanotubes with lengths greater than 8 μm were preferentially deposited. In addition, measured retention profiles exhibited the greatest MWCNT deposition near the column inlet, which was most pronounced for the long MWCNTs, and decreased sharply with travel distance. Scanning electron microscope (SEM) images showed that MWCNTs were deposited on sand surfaces over the entire column length, while larger MWCNT bundles were retained at grain intersections and near the column inlet. A mathematical model based on clean bed filtration theory (CBFT) was unable to accurately simulate the measured retention profile data, even after varying the weighting function and incorporating a nonuniform attachment rate coefficient expression. Modification of the mathematical model to account for physical straining greatly improved predictions of MWCNT retention, yielding straining rate coefficients that were four orders-of-magnitude greater than corresponding attachment rate coefficients. Taken in concert, these experimental and modeling results demonstrate the potential importance of, and need to consider, particle straining and tube length distribution when describing MWCNT transport in water-saturated porous media.
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► Functionalized MWCNT were readily transported through water-saturated quartz sand. ► MWCNT retention was elevated near the column inlet and longer tubes were preferentially retained. ► Scanning electron microscope (SEM) images provide direct evidence of physical straining. ► A clean- bed filtration theory (CBFT) model was unable to accurately simulate MWCNT retention profiles. ► Incorporation of a particle straining term greatly improved model predictions.
Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a ...chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.
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