Anti-cancer activity and cellular uptake of 7,3',4'- and 7,8,4'-trihydroxyisoflavone in HepG2 cells under hypoxic conditions.

Transarterial chemoembolisation (TACE) is used for unresectable hepatocellular carcinoma (HCC) treatment, but TACE-induced hypoxia leads to poor prognosis. The anti-cancer effects of soybean isoflavones daidzein derivatives 7,3',4'-trihydroxyisoflavone (734THIF) and 7,8,4'-trihydroxyisoflavone (784THIF) were evaluated under hypoxic microenvironments. Molecular docking of these isomers with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor receptor 2 (VEGFR2) was assessed. About 40 µM of 734THIF and 784THIF have the best effect on inhibiting the proliferation of HepG2 cells under hypoxic conditions. At a concentration of 40 µM, 784THIF significantly inhibits COX-2 expression in pre-hypoxia conditions compared to 734THIF, with an inhibition rate of 67.73%. Additionally, 40 µM 784THIF downregulates the expression of hypoxic, inflammatory, and metastatic-related proteins, regulates oxidative stress, and inhibits the expression of anti-apoptotic proteins. The uptake by HepG2 confirmed higher 784THIF level and slower degradation characteristics under post- or pre-hypoxic conditions. In conclusion, our results showed that 784THIF had better anti-cancer effects and cellular uptake than 734THIF.

Pterostilbene Nanoparticles Downregulate Hypoxia-Inducible Factors in Hepatoma Cells Under Hypoxic Conditions.

PURPOSE: Transcatheter arterial chemoembolization (TACE) is a common clinical treatment for hepatocellular carcinoma (HCC). However, hypoxia induction after treatment might trigger tumor invasiveness and metastasis. Although pterostilbene (PTS) has antitumor effects, its chemoprevention in HepG2 cells under hypoxia has not been investigated yet. In addition, the poor water solubility of raw PTS limits its clinical application. Here, we prepared nanoparticles of PTS (PSN) and compared their antihepatoma activities with those of raw PTS in HepG2 under hypoxic conditions. MATERIALS AND METHODS: The PTS nanoparticle formulation was prepared by nanoprecipitation, using Eudragit® e100 (EE) and polyvinyl alcohol (PVA) as carriers. We analyzed the physicochemical properties of raw PTS and PSN, including yield, encapsulation efficiency, water-solubility, particle size, morphology, crystalline-to-amorphous transformation, and molecular interaction between PTS and carriers. We also evaluated their antihepatoma activities under hypoxia treatment in HepG2 cells, including cell viability, hypoxia, and apoptosis. RESULTS: The yield and encapsulation efficiency of PSN were 86.33% and >99%, respectively. The water solubility and drug release of PTS were effectively improved after nanoprecipitation corresponding to the reduction in particle size, amorphous transformation, and formation of hydrogen bonding with carriers. PSN had a better cytotoxic effect than raw PTS in HepG2 under pre- and post-hypoxia conditions. In addition, hypoxia- and apoptosis-related proteins in HepG2 cells under two different hypoxic conditions were significantly inhibited by PSN compared with the control group with hypoxia only, except for HIF-1α in the post-hypoxia group. PSN was also significantly better in inhibiting these proteins, except for Bcl2, under pre-hypoxic conditions. CONCLUSION: Our results suggested that PSN could improve the water solubility and drug release of PTS and enhance the efficacy of HCC treatment under hypoxic conditions.

Inclusion complex of saikosaponin-d with hydroxypropyl-ß-cyclodextrin: Improved physicochemical properties and anti-skin cancer activity.

BACKGROUND: Saikosaponin-d (SSD) is a triterpene saponin isolated from Bupleurum plants. It has been shown to exhibit antioxidant, anti-inflammatory, and anticancer activities. However, its biomedical applications are limited by its poor water solubility. Cyclodextrins are highly water soluble oligosaccharide compounds which can form inclusion complexes with lipophilic drugs. PURPOSE: We complexed SSD with hydroxypropyl-ß-cyclodextrin (HPBCD) in various ratios to form SSD-HPBCD inclusion complexes. The inclusion complexes were evaluated for their solubility, physicochemical properties and cytotoxic effects in cutaneous squamous cell carcinoma cells. METHODS: Surface morphology of pure SSD and SSD-HPBCD inclusion complexes was evaluated by scanning electron microscopy. Crystalline structure was determined by X-ray diffractometry. Intermolecular hydrogen bond formation between SSD and HPBCD was investigated by Fourier transform infrared spectroscopy. Human cutaneous squamous cell carcinoma HSC-1 cell viability was determined by the MTS assay, and cell apoptosis by the caspase 3/7 assay. Signal transduction pathways were investigated by Western blotting. RESULTS: SSD-HPBCD inclusion complexes showed greatly increased water solubility. This was associated with an improvement in physicochemical properties, including transformation of crystalline structure to amorphous form, and formation of hydrogen bonds between SSD and HPBCD. In addition, SSD-HPBCD inclusion complexes induced apoptosis in HSC-1 cells, and this was mediated through activation of MAPK and suppression of Akt-mTOR signaling pathways. CONCLUSION: SSD-HPBCD inclusion complex shows improvement in water solubility and physicochemical properties, and exhibits anticancer effects against cutaneous squamous cell carcinoma cells. Therefore, it may be a potential drug formulation for the treatment of skin cancer.

Enhanced autophagic activity of artocarpin in human hepatocellular carcinoma cells through improving its solubility by a nanoparticle system.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Natural products offer great resources of developing new and effective chemopreventive or chemotherapeutic agents. Artocarpus communis extracts and its active constituent, prenylated flavonoid artocarpin induce human hepatocellular carcinoma cell death. However, the poor water solubility drawbacks of artocarpin restrict its clinical application and bioavailability. PURPOSE: This study developed the artocarpin nanoparticle system to overcome the poor water solubility drawbacks and investigated the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. METHODS: Antiproliferative activity of artocarpin was evaluated by MTT assay. Cell morphology observation by microscope, DNA fragmentation assay, cell cycle analysis, Annexin V apoptosis cell staining, monodansylcadaverine and acridine orange staining and immunoblot analysis were used to evaluate the induction of autophagy by artocarpin. The determination of particle size, amorphous transformation, hydrogen-bond formation, yield, encapsulation efficiency and the solubility study were used to investigate the solubility enhancement mechanism of artocarpin. RESULTS: The present study demonstrates that the anticancer effect of artocarpin in HepG2 and PLC/PRF/5 hepatoma cells is mediated through the autophagic cell death mechanism. Results also demonstrated that artocarpin nanoparticles enhanced the solubility of artocarpin by reducing particle size, transforming high energy amorphous state, and forming hydrogen bond with excipients. Additionally, ArtN exhibited better autophagic cytotoxicity compared to free artocarpin. CONCLUSION: This work reveals the antihepatoma activity of artocarpin by inducing autophagic cell death and the improvement of therapeutic efficacy of artocarpin by adopting novel nanoparticle delivery strategy. The research provided a basis of ArtN could be explored as a low-dose alternative of artocarpin in anticancer treatment and research applications.

Posteromedial olecranon impingement of the pitching elbow: Additional findings provided by CT.

PURPOSE: Posteromedial olecranon impingement (PMOI) is the most common diagnosis in baseball players with throwing-induced elbow injuries. CT imaging manifestations of PMOI have seldom been previously reported. Our purpose is to investigate the additional value of CT imaging in the evaluation of PMOI. MATERIALS AND METHODS: From July 2010 to December 2013, 47 baseball players with throwing-induced elbow pain received imaging studies (CT and/or MRI) of the elbow at our institution. After retrospectively reviewing the clinical records and imaging studies, 31 of the 47 players were diagnosed with PMOI by the criteria of posteromedial elbow pain with clinical consistency for PMOI and characteristic osteoarthrosis at the posteromedial ulnotrochlear articulation (posteromedial olecranon space, PMOS) detected by CT and/or MRI. The imaging modalities of these 31 players including radiography, CT, and MRI were reviewed by 2 experienced musculoskeletal radiologists. RESULTS: The most common imaging manifestations of PMOI by CT or MRI include joint space narrowing, subchondral sclerosis, and osteophytes at the PMOS. CT was superior to MRI with a statistically significant (P<0.05) difference in detecting joint space narrowing, medial olecranon subluxation, as well as the number of loose bodies. In contrast, bone marrow edema and associated soft tissue injuries in PMOI are more readily observed on MRI. CONCLUSIONS: CT is superior in identifying some imaging features of PMOI. Whenever PMOI is diagnosed in the pitching elbow of a baseball player, CT should be considered prior to surgical intervention as it will often provide additional information to the surgeon that may alter surgical management.

An Effective and Well Tolerated Strategy of Bladder Preservation Therapy in Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer.

UNLABELLED: To investigate bladder preservation therapy with a well tolerated strategy, 30 patients with bladder cancer underwent concomitant chemoradiotherapy with weekly carboplatin. The 2-year overall survival was 75% for all patients, 43% and 95% for patients without adjuvant chemotherapy or with adjuvant chemotherapy separately. This strategy was well tolerated with 7% of Grade 3/4 late bladder toxicity. BACKGROUND: The purpose of this study was to determine the feasibility and clinical effectiveness of concurrent weekly carboplatin chemotherapy in conjunction with definite radiation with or without adjuvant chemotherapy in the treatment of muscle-invasive bladder cancer. PATIENTS AND METHODS: Between April 2010 and December 2013, 30 patients with muscle-invasive bladder cancer were evaluated retrospectively in this study. Concurrent chemoradiotherapy (CCRT) with weekly carboplatin was initiated. CCRT was followed by 2 courses of carboplatin and gemcitabine limited to patients with Eastern Cooperative Oncology Group performance status < 3 and age < 80 years. RESULTS: Thirty patients were treated and all completed the CCRT protocol. Seven of 8 patients (88%) achieved a pathological complete response (pCR) with CCRT alone, and 18 of 22 patients (82%) treated with CCRT followed by adjuvant chemotherapy had a pCR. The median follow-up was 23.2 (range, 8.3-40.7) months. The median progression-free survival was 15.9 months for the CCRT group, and not sufficient to evaluate CCRT followed by adjuvant chemotherapy. The median overall survival with CCRT was 18.8 months, and had not yet been reached for CCRT with adjuvant chemotherapy. The protocol was well tolerated for adverse events. CONCLUSION: Our study has shown that concomitant chemotherapy using weekly carboplatin in the management of muscle-invasive bladder cancer is feasible and well tolerated, even in older patients. Additional adjuvant chemotherapy with 2 cycles of carboplatin and gemcitabine should be encouraged in physically fit patients. These results provide a basis for randomized studies to compare this approach with conventional therapy for patients who wish to preserve the bladder.

Do ePortfolios Contribute to Learners' Reflective Thinking Activities? : A Preliminary Study of Nursing Staff Users.

The purposes of this study are threefold: 1) to find out what characteristics are required for the successful use of ePortfolios; 2) to discover what activities best represent reflective thinking during the use of ePortfolios; and, 3) to investigate the interrelationship between nursing staff users' perceived success levels with ePortfolios and with their reflective thinking activities. Survey methodology was used to gather responses from 78 nurses from a medical center located in southern Taiwan via questionnaires. Factor analysis and canonical correlation analysis were used to analyze the collected data. The results demonstrated that system quality, information quality, and user satisfaction are important variables in successful ePortfolio usage; while habitual action, understanding, reflection, and critical reflection are major variables of reflective thinking. Further, we found a significant relationship exists between the relative success of ePortfolios and reflective thinking activities of ePortfolios users. The subject hospital should pay special attention to important characteristics including system quality, information quality, and user satisfaction when employing ePortfolios to help nursing staff users to achieve their learning goals through this form of reflective thinking.

Artocarpus communis Induces Autophagic Instead of Apoptotic Cell Death in Human Hepatocellular Carcinoma Cells.

For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.

Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content.

Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract.

A socio-technical assessment of the success of Picture Archiving and Communication Systems: the radiology technologist's perspective.

BACKGROUND: With the increasing prevalence of Picture Archiving and Communication Systems (PACS) in healthcare institutions, there is a growing need to measure their success. However, there is a lack of published literature emphasizing the technical and social factors underlying a successful PACS. METHODS: An updated Information Systems Success Model was utilized by radiology technologists (RTs) to evaluate the success of PACS at a large medical center in Taiwan. A survey, consisting of 109 questionnaires, was analyzed by Structural Equation Modeling. RESULTS: Socio-technical factors (including system quality, information quality, service quality, perceived usefulness, user satisfaction, and PACS dependence) were proven to be effective measures of PACS success. Although the relationship between service quality and perceived usefulness was not significant, other proposed relationships amongst the six measurement parameters of success were all confirmed. CONCLUSIONS: Managers have an obligation to improve the attributes of PACS. At the onset of its deployment, RTs will have formed their own subjective opinions with regards to its quality (system quality, information quality, and service quality). As these personal concepts are either refuted or reinforced based on personal experiences, RTs will become either satisfied or dissatisfied with PACS, based on their perception of its usefulness or lack of usefulness. A satisfied RT may play a pivotal role in the implementation of PACS in the future.

An unusual appearance of renal epithelioid angiomyolipoma.

Epithelioid angiomyolipoma is a recently described rare variant of renal angiomyolipoma. It can occur in patients with or without tuberous sclerosis. We report the imaging findings of a case of epithelioid angiomyolipoma that showed the presence of fatty tissue undifferentiated from the typical angiomyolipoma at the beginning. After partial nephrectomy, tumour recurrence occurred two years later, presenting as completely solid tumours with no adipose tissue, and with invasion into the psoas muscle and left adrenal gland. Differentiation of this tumour from renal cell carcinoma is difficult. Both the radiologist and surgeon should be aware of the existence of this tumour and its potentially malignant behaviour.

Imaging features of posterior limbus vertebrae.

Posterior limbus vertebra (PLV) is the retropulsion of the vertebral ring apophysis resulting from disc herniation through posterior ring physis. Large PLV can cause spinal stenosis, and small PLV can be mistaken as intraspinal disc herniation. Although the clinical presentations were similar, the surgery was quite different. We had experienced preoperative misdiagnosed cases and the surgery could not be finished. Therefore we analyzed the imaging features of PLV in 34 patients in order to prompt appropriate preoperative diagnosis and surgical planning.

A comparison of pyelography and various reconstructions of multidetector helical computed tomography urography images for diagnosing urinary obstruction.

Radiologists and urologists require practical and helpful image reconstructions for diagnosing urinary obstruction. We performed different types of imaging and reconstruction, then used a self-designed urinary obstruction-specific questionnaire to evaluate the diagnostic outcome of them. Our results suggested that two-dimensional (2D) axial computed tomography (CT) is clinically superior to retrograde pyelography or antegrade pyelography, and to other modes of image reconstruction that are often used for diagnosing urinary obstruction.

Comprehensive MDCT evaluation of patients with suspected May-Thurner syndrome.

OBJECTIVE: The purpose of this essay is to introduce the MDCT protocol and interpretation techniques for optimal evaluation of patients with suspected May-Thurner syndrome. CONCLUSION: May-Thurner syndrome is always the working diagnosis when a patient presents with unilateral left lower limb swelling without signs of infection. MDCT is useful for fast, comprehensive evaluation of the vascular system to determine whether May-Thurner syndrome or an alternative condition is present.

Resveratrol nanoparticle system improves dissolution properties and enhances the hepatoprotective effect of resveratrol through antioxidant and anti-inflammatory pathways.

Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound, is abundant in red wine and exerts numerous pharmacological effects, including hepatoprotection and cadioprotection. Unfortunately, RES is restricted in clinical application due to poor dissolution property and adsorption. In addition, red wine as a supplement for preventing disease is not recommended for patients with alcohol-related disorders. To address these limitations, we successfully developed a novel RES nanoparticle system (RESN) and demonstrated that RESN could circumvent the physicochemical drawbacks of raw RES with respect to dissolution, such as the reduction of particle size, amorphous transformation, and hydrogen-bond formation. In addition, we employed an animal model of CCl4-induced hepatotoxicity to estimate the potential of the nanoparticle formulation to improve the hepatoprotective effect of orally administered RES. Our results demonstrated that RESN can diminish liver function markers (aspartate aminotransferase and alanine aminotransferase) by decreasing hepatocyte death due to CCl4-induced hepatotoxicity in rats, when compared with RES administration. The effect was achieved by reducing oxidative stress (decreased reactive oxygen species and lipid peroxidation) and lowering inflammatory cytokines (decreased tumor necrosis factor-α and interleukin 1ß) and protein expression (cyclooxygenase-2, inducible nitric oxide synthase, cytosolic phospholipase A2, and caspase-3). In conclusion, enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases.