Cardiovascular Events According to Inhaler Therapy and Comorbidities in Chronic Obstructive Pulmonary Disease.

Background: COPD coexists with many concurrent comorbidities. Cardiovascular complications are deemed to be major causes of death in COPD. Although inhaler therapy is the main therapeutic intervention in COPD, cardiovascular events accompanying inhaler therapy require further investigation. Therefore, this study aimed to investigate new development of cardiovascular events according to each inhaler therapy and comorbidities. Methods: This study analyzed COPD patients (age ≥ 40 years, N = 199,772) from the Health Insurance Review and Assessment Service (HIRA) database in Korea. The development of cardiovascular events, from the index date to December 31, 2020, was investigated. The cohort was eventually divided into three arms: the LAMA/LABA group (N = 28,322), the ICS/LABA group (N = 11,812), and the triple group (LAMA/ICS/LABA therapy, N = 6174). Results: Multivariable Cox analyses demonstrated that, compared to ICS/LABA therapy, triple therapy was independently associated with the development of ischemic heart disease (HR: 1.22, 95% CI: 1.04-1.43), heart failure (HR: 1.45, 95% CI: 1.14-1.84), arrhythmia (HR: 1.72, 95% CI: 1.41-2.09), and atrial fibrillation/flutter (HR: 2.31, 95% CI: 1.64-3.25), whereas the LAMA/LABA therapy did not show a significant association. Furthermore, emergency room visit during covariate assessment window was independently associated with the development of ischemic heart disease, heart failure, arrhythmia, and atrial fibrillation/flutter (p < 0.05). Conclusion: Our data suggest that cardiovascular risk should be considered in COPD patients receiving triple therapy, despite the confounding bias resulting from disparities in each group.

Sorafenib versus nivolumab after lenvatinib treatment failure in patients with advanced hepatocellular carcinoma.

BACKGROUND AND AIM: An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. METHODS: Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. RESULTS: The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). CONCLUSIONS: Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2.

The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half1 ( https://www.who.org/ ). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clinical outcomes2. Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approximately 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogues, the largest category of clinically used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogues synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clinical path forward.

Predictive Performance of CAGE-B and SAGE-B Models in Asian Treatment-Naive Patients Who Started Entecavir for Chronic Hepatitis B.

BACKGROUND & AIMS: Cirrhosis and age (CAGE-B) and stiffness and age (SAGE-B) models assess the risk of hepatocellular carcinoma (HCC) development in white patients with chronic hepatitis B (CHB) undergoing sustained antiviral therapy (AVT). Herein, we checked the predictive performance of these models in Asian patients with CHB. METHODS: We reviewed 734 treatment-naive patients with CHB who started entecavir between 2006 and 2011 and were followed up for more than 5 years without HCC development during AVT. The predictive performance of CAGE-B and SAGE-B models was calculated using area under the receiver operating characteristic curves (AUROCs). RESULTS: Median liver stiffness assessed using transient elastography after 5 years of AVT was 6.8 kPa. Median CAGE-B and SAGE-B models after 5 years of AVT were 7.0 and 6.0, respectively. More than 5 years after AVT initiation, 66 patients (9.0%) developed HCC. The AUROCs of the CAGE-B and SAGE-B models were 0.764 and 0.785 after 7 years and 0.799 and 0.802 after 10 years of AVT, respectively. The cumulative incidence of HCC was significantly higher in the high-risk groups according to CAGE-B and SAGE-B risk stratification than in the medium- and low-risk groups (P < .05 in all cases). The SAGE-B model showed a higher likelihood ratio (χ2) (76.2 vs 71.4) and linear trend (χ2) (74.1 vs 58.6) than the CAGE-B model, whereas the CAGE-B model showed higher Akaike information criteria (64.3 vs 50.3). CONCLUSIONS: Both SAGE-B and CAGE-B showed acceptable performance in predicting HCC after 5 years of AVT in Asian patients with CHB.

Treatment efficacy by hepatic arterial infusion chemotherapy vs. sorafenib after liver-directed concurrent chemoradiotherapy for advanced hepatocellular carcinoma.

BACKGROUND: We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC). METHODS: Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates. RESULTS: The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group. CONCLUSIONS: The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.

Effects of treatment with long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) on lung function improvement in patients with bronchiectasis: an observational study.

BACKGROUND: Patients with bronchiectasis are often treated with bronchodilators such as long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists (LABA) for their symptoms, but empirical evidence supporting such practice is sparse. We evaluated the effect of LAMA and LABA on lung function improvement in patients with bronchiectasis. METHODS: Using the in-house patient database at a tertiary referral hospital in Seoul, South Korea, we extracted data from patients diagnosed as bronchiectasis with computed tomography (CT) scan and treated with LAMA, LABA, or both. Patients with asthma, chronic obstructive pulmonary disease (COPD) or a history of cigarette smoking were excluded, and a subgroup analysis was performed in patients who did not receive concurrent treatments such as antibiotics, mucolytics or systemic steroids that may affect lung function improvement. RESULTS: A total of 230 patients (males: 32.6%, median age: 60 years) were analyzed. Their mean forced expiratory volume in 1 second (FEV1) was 53.3% of the predicted value [standard deviation (SD), 15.3]. The patients received LAMA (n=95), LABA (n=36), or both (LAMA-LABA; n=99), after which their FEV1 values were increased by 0.102 liters (SD, 0.208; P<0.001), 0.133 liters (SD, 0.181; P<0.001), and 0.122 liters (SD, 0.230; P<0.001), respectively. In a subgroup of 97 patients who did not receive concurrent treatments, the FEV1 was increased by with 0.107 liters (SD, 0.167; P<0.001), 0.165 liters (SD, 0.209; P=0.005), and 0.165 liters (SD, 0.187; P<0.001) in the LAMA, LABA, and LAMA-LABA groups, respectively. Baseline FEV1 had a significant negative correlation with response to bronchodilator treatment in the total patient cohort (R=-0.242, P<0.001) and the subgroup of patients without concurrent treatments (R=-0.386, P<0.001). CONCLUSIONS: Treatment with bronchodilators such as LAMA or LABA was effective in improving lung function in patients with bronchiectasis, regardless of concurrent treatments that also improve lung function. These data may support the use of LAMA and LABA in patients with bronchiectasis.

A survey on transarterial chemoembolization refractoriness and a real-world treatment pattern for hepatocellular carcinoma in Korea.

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC), but there is much controversy about TACE refractoriness. The aim of this study was to identify trends in the actual clinical application of TACE and recognition of TACE refractoriness by Korean experts. METHODS: In total, 17 questionnaires on TACE refractoriness were administered to 161 clinicians via an online survey. Multiple answers were allowed for some questions. RESULTS: Most clinicians agreed that there is a need for standardization of TACE application through specific scoring systems (n=124, 77.0%). TACE refractoriness was predominantly expected by participants when recurrences were detected within 1 month (n=70, 43.5%), there were 4 to 6 tumors (n=77, 47.8%), the maximal tumor size was 3-5 cm (n=49, 30.4%), and when there was insufficient tumor necrosis despite TACE being repeated more than three times (n=78, 48.4%). Overall, sorafenib therapy (n=137) and radiotherapy (n=114) were preferred when repeated TACE was considered ineffective. CONCLUSION: Treatment of HCC is often based on the clinical judgment of clinicians because of the heterogeneity among individuals. Experts need to continue discussions on the standardization and sub-classification of HCC treatment guidelines in Korea.

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers.

OBJECTIVES: Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. METHODS: The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. RESULTS: During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). CONCLUSION: In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer.

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031-3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

In Vitro MIC Values of Rifampin and Ethambutol and Treatment Outcome in Mycobacterium avium Complex Lung Disease.

Although it is known that the in vitro MICs of rifampin and ethambutol are poorly correlated with the clinical response in Mycobacterium avium complex (MAC) lung disease (MAC-LD), evidence for this is limited. This study investigated the association between treatment outcome and the in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients who were treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MICs of antimicrobial agents were determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and tended to decrease with increasing MICs of rifampin and ethambutol, particularly at MICs of ≥8 µg/ml. Treatment success rate was significantly different between MAC isolates with MICs of ≥8 µg/ml for rifampin and ethambutol and those with MICs of <8 µg/ml for rifampin and/or ethambutol (64.9% versus 85.3%, P < 0.001). Multivariate analysis showed that an MIC of ≥8 µg/ml for both drugs and initial sputum acid-fast bacillus (AFB) smear positivity were independent risk factors for an unfavorable response (adjusted odds ratio [OR] = 3.154, 95% confidence interval [CI] = 1.641 to 6.063, and P = 0.001 for an MIC of ≥8 µg/ml; adjusted OR = 2.769, 95% CI = 1.420 to 5.399, and P = 0.003 for initial sputum AFB smear positivity). These findings suggest that the in vitro MICs of rifampin and ethambutol may be related to treatment outcome in MAC-LD.

Predicting treatable traits for long-acting bronchodilators in patients with stable COPD.

PURPOSE: There is currently no measure to predict a treatability of long-acting ß-2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) in patients with chronic obstructive pulmonary disease (COPD). We aimed to build prediction models for the treatment response to these bronchodilators, in order to determine the most responsive medication for patients with COPD. METHODS: We performed a prospective open-label crossover study, in which each long-acting bronchodilator was given in a random order to 65 patients with stable COPD for 4 weeks, with a 4-week washout period in between. We analyzed 14 baseline clinical traits, expression profiles of 31,426 gene transcripts, and damaged-gene scores of 6,464 genes acquired from leukocytes. The gene expression profiles were measured by RNA microarray and the damaged-gene scores were obtained after DNA exome sequencing. Linear regression analyses were performed to build prediction models after using factor and correlation analyses. RESULTS: Using a prediction model for a LABA, traits found associated with the treatment response were post-bronchodilator forced expiratory volume in 1 second, bronchodilator reversibility (BDR) to salbutamol, expression of three genes (CLN8, PCSK5, and SKP2), and damage scores of four genes (EPG5, FNBP4, SCN10A, and SPTBN5) (R2=0.512, p<0.001). Traits associated with the treatment response to a LAMA were COPD assessment test score, BDR, expression of four genes (C1orf115, KIAA1618, PRKX, and RHOQ) and damage scores of three genes (FBN3, FDFT1, and ZBED6) (R2=0.575, p<0.001). The prediction models consisting only of clinical traits appeared too weak to predict the treatment response, with R2=0.231 for the LABA model and R2=0.121 for the LAMA model. CONCLUSION: Adding the expressions of genes and damaged-gene scores to the clinical traits may improve the predictability of treatment response to long-acting bronchodilators.

Improvement in Ventilation-Perfusion Mismatch after Bronchoscopic Lung Volume Reduction: Quantitative Image Analysis.

Purpose To evaluate whether bronchoscopic lung volume reduction (BLVR) increases ventilation and therefore improves ventilation-perfusion (V/Q) mismatch. Materials and Methods All patients provided written informed consent to be included in this study, which was approved by the Institutional Review Board (2013-0368) of Asan Medical Center. The physiologic changes that occurred after BLVR were measured by using xenon-enhanced ventilation and iodine-enhanced perfusion dual-energy computed tomography (CT). Patients with severe emphysema plus hyperinflation who did not respond to usual treatments were eligible. Pulmonary function tests, the 6-minute walking distance (6MWD) test, quality of life assessment, and dual-energy CT were performed at baseline and 3 months after BLVR. The effect of BLVR was assessed with repeated-measures analysis of variance. Results Twenty-one patients were enrolled in this study (median age, 68 years; mean forced expiratory volume in 1 second [FEV1], 0.75 L ± 0.29). After BLVR, FEV1 (P < .001) and 6MWD (P = .002) improved significantly. Despite the reduction in lung volume (-0.39 L ± 0.44), both ventilation per voxel (P < .001) and total ventilation (P = .01) improved after BLVR. However, neither perfusion per voxel (P = .16) nor total perfusion changed significantly (P = .49). Patients with lung volume reduction of 50% or greater had significantly better improvement in FEV1 (P = .02) and ventilation per voxel (P = .03) than patients with lung volume reduction of less than 50%. V/Q mismatch also improved after BLVR (P = .005), mainly owing to the improvement in ventilation. Conclusion The dual-energy CT analyses showed that BLVR improved ventilation and V/Q mismatch. This increased lung efficiency may be the primary mechanism of improvement after BLVR, despite the reduction in lung volume. © RSNA, 2017 Online supplemental material is available for this article.

α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrate L. (syn. E. alba Hassk), commonly known as False Daisy, has been used in traditional medicine in Asia to treat a variety of diseases, including cancer. Although an anti-tumor effect has been suggested for E. prostrata, the exact anti-tumor effects and underlying molecular mechanisms of its bioactive compounds are poorly understood. The aim of this study was to identify compounds with anti-cancer activity from E. prostrata and to investigate their mechanism of action. MATERIALS AND METHODS: To assess cell viability, cell cycle progression, and apoptosis, we performed MTT assays and FACS analysis using Annexin and PI staining. We also investigated reactive oxygen species (ROS) production and caspase activation using flow cytometry and Western blot analysis, respectively. Cytosolic translocation of cytochrome c was measured using an ELISA kit. Antioxidants, MAPK signaling inhibitors, NADPH oxidase inhibitors, and siRNA were used to elucidate the molecular mechanism of action of the compound. RESULTS: We isolated five terthiophenes from the n-hexane fraction of E. prostrata; of these, α-terthienylmethanol possessed potent cytotoxic activity against human endometrial cancer cells (Hec1A and Ishikawa) (IC50<1µM). The growth inhibitory effect of α-terthienylmethanol was mediated by the induction of apoptosis, as shown by the accumulation of sub-G1 and apoptotic cells. In addition, α-terthienylmethanol triggered caspase activation and cytochrome c release into the cytosol in a time-dependent manner. Moreover, α-terthienylmethanol increased the intracellular level of ROS and decreased that of GSH, and the antioxidants N-acetyl-l-cysteine and catalase significantly attenuated α-terthienylmethanol-induced apoptosis. We further demonstrated that inhibition of the NADPH oxidase attenuated α-terthienylmethanol-induced cell death and ROS accumulation in endometrial cancer cells. CONCLUSION: Overall, these results suggest that α-terthienylmethanol, a naturally occurring terthiophene isolated from E. prostrata, induces apoptosis in human endometrial cancer cells by ROS production, partially via NADPH oxidase.

Constituents of the aerial parts of Eclipta prostrata and their cytotoxicity on human ovarian cancer cells in vitro.

A new terthiophene, 3'-hydroxy-2,2':5',2″-terthiophene-3'-O-ß-D-glucopyranoside (1) and a new oleanane-type saponin, echinocystic acid-3-O-(6-O-acetyl)-ß-D-glucopyranoside (7) were isolated from the aerial parts of Eclipta prostrata L. Moreover, five thiophenes (2-6), seven triterpenoids (8-14), two coumestans (15 and 16), and four flavonoids (17-20) having previously known chemical structures were isolated during the same course of this study. All the isolates 1-20 were evaluated for their cytotoxicity against human ovarian cancer cells (SKOV3) using MTT assays.

Real-time phase-contrast imaging of photothermal treatment of head and neck squamous cell carcinoma: an in vitro study of macrophages as a vector for the delivery of gold nanoshells.

Photothermal treatment (PTT) using nanoparticles has gained attention as a promising alternative therapy for malignant tumors. One strategy for increasing the selectivity of PTT is the use of macrophages as a cellular vector for delivering nanoparticles. The aim of the present study is to examine the use of macrophages as a cellular vector for efficient PTT and determine the appropriate irradiation power and time of a near-infrared (NIR) laser using real-time phase-contrast imaging. Thermally induced injury and death of cancer cells were found to begin at 44°C to 45°C, which was achieved using the PTT effect with gold nanoshells (NS) and irradiation with a NIR laser at a power of 2 W for 5 min. The peritoneal macrophage efficiently functioned as a cellular vector for the NS, and the cancer cells surrounding the NS-loaded macrophages selectively lost their cellular viability after being irradiated with the NIR laser.