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Abstract Grifola frondosa is a widely eaten and medicinal fungus. In this study, we extracted a cold-water-soluble polysaccharide from Grifola frondosa (cGFP) and investigated its effects on the proliferation and apoptosis of human hepatoma HepG2 cells. MTT assay showed that cGFP induced apoptosis of HepG2 cells in a dose-dependent manner. Flow cytometry analysis showed that cGFP induced apoptosis in HepG2 cells through S phase arrest. The distribution of cells at different apoptotic stages was determined by Annexin V-FITC and Propidium Iodide (PI) staining. Scanning electron microscopy (SEM) results indicated that cGFP induced typical apoptotic morphological features in HepG2. Mitochondrial membrane potential was reduced according to the screening of JC-1 staining. And western blot analysis of Bax, Bcl-2, cytochrome C (Cyto-c), caspase-3, and caspase-9 further demonstrated that the cGFP-induced apoptosis effect functioned through the mitochondrial pathway. Further analysis by qRT-PCR showed that Bax expression increased and Bcl-2 expression decreased. These findings suggested that cGFP could inhibit the proliferation of HepG2 cells and induce apoptosis mainly through the intrinsic activation mitochondrial pathway. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a typical flavonoid compound derived from the plant Curcuma longa, has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including antioxidant, anti-inflammatory and antiseptic activities. More recently curcumin has been found to possess anticancer activities by acting on multiple intracellular signaling network molecules. However, multidrug resistance (MDR) mediated by P-gp, MRP1, LRP and BCRP is a major obstacle to the effective treatment of cancer. Currently, research has step towards reversing MDR by using curcumin. This review will summarize the MDR mechanisms and the new points on the regulation of MDR protein expression and function by curcumin. The current in vitro and in vivo data related to the MDR reversing activity of curcumin in human cancers as well as the accurate mechanisms concerning curcumin as an adjuvant chemotherapeutic reversal agent have also been discussed in brief. [Copyright &y& Elsevier]

Background/purpose: Percutaneous cryotherapy has become a minimally invasive treatment option for unresectable lung malignancies. We report the experience and outcomes with percutaneous computed tomography (CT)-guided cryotherapy of primary lung malignancies, as well as recurrence and metastases, in patients ineligible for surgery.Methods: The procedure was performed after administration of local anesthesia on 23 tumors in 19 patients (10 male and 9 female patients; mean age, 58.7 years). None of the patients were surgical candidates and underwent CT-guided percutaneous cryotherapy for treatment of the malignant mass in the lung. Visualization of low-attenuation ice ball formation was performed using CT scanning after each cycle of freezing and thawing therapy. Subsequent CT scans were scheduled at 3-month intervals post-procedure to assess tumor control.Results: No lethal complication, major bleeding or bronchial damage was observed in any of the 23-cryotherapy sessions performed. Three patients developed pneumothorax and one patient required chest tube insertion. Thirteen tumors (56.5%) regressed, including two complete responses, five tumors (21.7%) were stationary and the remaining five tumors (21.7%) were found to be progressing at the 3-month follow-ups. No recurrence was found in the 11 regressed tumors for 6 months, and there was also no recunence in the two tumors that completely responded up to 12 months later with a satisfactory procedure.Conclusion: Percutaneous cryotherapy for primary lung cancer, recurrence and metastatic lung tumors is feasible and safe for local control. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to evaluate the performance of transtracheal thoracic exploration and pericardial window creation in a canine survival model. Methods: Transthoracic exploration was performed in 14 dogs. Under general anesthesia, after an incision in the right lateral wall of the middle–lower portion of the trachea was made, a 9-mm metal tube was advanced into the thoracic cavity. For thoracic cavity exploration and pericardial window creation, a flexible bronchoscope was introduced through the metal tube into the thoracic cavity. After thoracoscopy, a Dumon stent (Novatech, Grasse, France) was used to cover the tracheal incision site and facilitate healing. Animals were evaluated by endoscopy 1 and 2 weeks later. Animals were humanely killed, and necropsy was performed 2 weeks after the transtracheal natural orifice transluminal endoscopic surgery. Results: Fourteen dogs underwent transtracheal thoracic exploration lasting for an average of 110 minutes (range, 80–150), with 3 perioperative deaths. At 2 weeks after pericardial window creation, endoscopy revealed normal healing of the tracheal incision sites in all 11 surviving animals. Necropsy on the 11 animals at 2 weeks showed 9 adhesions around the pericardial window and 5 adhesions around the tracheal incision region. No mediastinitis or abscesses could be identified. Conclusions: Transtracheal thoracic exploration is technically feasible. Increasing surgical experience together with improvement in endoscopic techniques will further facilitate the development of natural orifice transluminal endoscopic surgery for thoracic diseases. [Copyright &y& Elsevier]

Abstract: LiFePO4/C composite cathode material was prepared by carbothermal reduction method, which uses NH4H2PO4, Li2CO3 and cheap Fe2O3 as starting materials, acetylene black and glucose as carbon sources. The precursor of LiFePO4/C was characterized by differential thermal analysis and thermogravimetry. X-ray diffraction (XRD), scanning electron microscopy (SEM) micrographs showed that the LiFePO4/C is olivine-type phase, and the addition of the carbon reduced the LiFePO4 grain size. The carbon is dispersed between the grains, ensuring a good electronic contact. The products sintered at 700°C for 8h with glucose as carbon source possessed excellent electrochemical performance. The synthesized LiFePO4 composites showed a high electrochemical capacity of 159.3mAhg−1 at 0.1C rate, and the capacity fading is only 2.2% after 30 cycles. [Copyright &y& Elsevier]

Summary: To evaluate the association of epidermal growth factor receptor (EGFR) gene copy number with EGFR and k-ras mutation status and tyrosine kinase inhibitor (TKI) sensitivity in non-small cell lung cancer (NSCLC), EGFR gene copy number of 182 NSCLC tumor specimens were analyzed by chromogenic in situ hybridization (CISH). EGFR and k-ras mutation analyses were also performed for, respectively, 176 and 157 of the 182 patients. Additionally, 36 patients in this study had received TKI monotherapy. The tumor was considered to be CISH positive if the gene copy number was ≥5 signals per nucleus in ≥40% of tumor cells. CISH-positive tumors were strongly associated with adenocarcinoma (56.8%) compared with squamous cell carcinoma (15.9%) (p <0.0001). The CISH-positive tumors were also strongly associated with EGFR mutations (78%) compared with wild type (20.2%) (p <0.0001). Only six tumors had k-ras mutations. None had EGFR mutation and only one was CISH positive. In the patients treated with TKI, EGFR mutation was strongly associated with TKI responsiveness (22/25 responders) (p <0.0001), but the CISH-positive tumors were only marginally significant (18/25 responders) (p =0.0665). Patients with EGFR mutations or CISH-positive tumors were all associated with longer median survival, although not statistically significant. Our results suggest Increased EGFR copy number was highly correlated with EGFR mutation in adenocarcinoma. Although it is less correlated with TKI responsiveness when compared with EGFR mutations, it still could be a good alternative molecular predictive marker for TKI responsiveness, since CISH can be done on paraffin section and is much quicker than DNA sequencing. [Copyright &y& Elsevier]

Abstract: Objective: Pneumothorax (PTX) after trauma is a preventable cause of death. Drainage procedures such as chest tube insertion have been traditionally advocated to prevent fatal tension PTX. We evaluated the safety of close observation in patients with delayed PTX complicating rib fracture after minor chest trauma. Materials and Methods: Adult patients (>18 years) with a diagnosis of chest trauma and 3 or fewer fractured ribs were reviewed. Case patients were divided according to age, location and number of fractured ribs, mechanism of trauma, and initial pulmonary complication after thoracic trauma for comparative analysis. Results: There were 207 male (70.2%) and 88 female (29.8%) patients whose ages ranged from 18 to 93 years (median, 55 years). The mechanisms of trauma were a motor vehicle accident in 207 patients, falls in 66, pedestrian injury in 10, and assaults in 14. Ninety-five patients sustained 1 rib fracture, 95 had 2 rib fractures, and 105 suffered 3 rib fractures. Right-sided injury occurred in 164 cases, left-sided injury did in 127, and bilateral injury did in 4. The most frequent location of rib fractures was from the fourth rib to the ninth rib. The initial pulmonary complications after trauma were PTX in 16 patients, hemothorax in 43, pneumohemothorax in 14, lung contusion in 75, and isolated subcutaneous emphysema (SubcEmph) in 33. Thirty percent of the patients (n = 5/16) who presented with traumatic PTX were observed safely without drainage. Delayed PTX was recorded in 16 patients, occurring mostly during the first 2 days of their admission. Associated extrathoracic injury was recorded in 189 patients. The mean hospital stay of the patients was 7.66 days. Longer hospital stay was related to increasing number of fractured ribs, need for thoracic drainage, and the presence of associated extrathoracic injury. The mortality rate for the entire group was 2%. The presence of SubcEmph was the only risk factor associated with the development of delayed PTX. Conclusions: Patients sustaining blunt chest trauma and minor rib fractures should be admitted for close observation when presenting with SubcEmph because of possible delayed presentation of PTX. [Copyright &y& Elsevier]

Background/purpose: Histologic diagnosis of suspicious small subpleural lung lesions is difficult and often impossible using existing image-guided needle biopsy techniques including video-assisted thoracoscopic wedge resection. Preoperative lung lesion localization provides a more obvious target to facilitate intraoperative resection. This study reviewed the indications, results and complications of CT-guided hook wire localization for subpleural lung lesions in video-assisted thoracoscopic surgery (VATS).Methods: Between February 2001 and January 2007, 41 patients (20 males, 21 females; mean age, 52.5 +/- 5.1 years) with 43 subpleural pulmonary lesions underwent preoperative CT-guided double-thorn hook wire localization prior to video-assisted thoracoscopic wedge resection. Nodule diameters ranged from 2 mm to 26 mm (mean, 9.7 +/- 1.6 mm). The distance of the lung lesions from the nearest pleural surfaces ranged from 2 mm to 30 mm (mean, 9.6 +/- 2.0 mm). Patients then received VATS within 5 hours. The efficacy of preoperative localization was evaluated in terms of procedure time, VATS success rate and associated complications of localization.Results: Forty-three wedge resections of the lungs containing 43 subpleural lung lesions as guided or assisted by the inserted hook wires were successfully performed in 41 VATS procedures (41 of 43 procedures, 95.3%). The mean procedure time for preoperative CT-guided hook wire localization was 30.4 +/- 2.8 minutes. Eight patients had asymptomatic minimal pneumothoraces (18.6%); six patients had minimal needle tract parenchymal hemorrhages (13.9%) and one patient (2.3%) had an estimated 100 mL of hemothorax due to a small intercostal artery bleed that was cauterized during operation. The mean procedure time for VATS was 103 +/- 9.7 minutes (range, 44-198 minutes). Pathologic examination revealed seven primary lung cancers, 11 metastases, one hemangioma, 19 definite non-neoplastic pathologies, two nonspecific chronic inflammation, and three metallic foreign bodies. Diagnostic yield was 95%. No major complications related to the preoperative hook wire localization and VATS were noted.Conclusion: CT-guided hook wire fixation is useful, helps in precise lesion localization in VATS wedge resection, and has a low rate of minor complications. [ABSTRACT FROM AUTHOR]

Abstract: First-principle calculations are performed for the study of Rb2Cd2(SO4)3 langbeinites. Electronic bands, joint and partial densities of states as well as charge density distribution are analyzed systematically. We find that because oxygen atomic 2p electrons strongly hybridize with Rb or Cd 4d and S 2p states, there exist two-type ionic groups in the langbeinite structures. The couple strength between the cation bonds and the SO4 tetrahedra in the monoclinic phase is stronger than that in the orthorhombic. Hybridization effects of 4d electrons are the origin of monoclinic paraelectricity and orthorhombic ferroelectricity, relating to atomically shape domain wall rotations. As a result, the asymmetric cation bonds (Rbce:glyph name="sbnd" />O) and the subsequent rotations of the SO4 tetrahedra can lead to the driving force of the ferroelectric behaviors. It is shown that atomically shape domain walls originate from such coupling ionic groups, arising at the cell boundaries. The predicted pyroelectric current effects were observed experimentally in the ferroelectric phase. [Copyright &y& Elsevier]

Background. Free deepithelialized anterolateral thigh (DALT) flaps have been used for treatment of chronic intractable empyema with bronchopleural fistula at Chang Gung Memorial Hospital since 1997.Methods. Twelve patients with chronic empyema were treated at Chang Gung Memorial Hospital from January 1997 to January 2001. Their age ranged from 31 to 70 years (mean age 48.6 years). Left-sided involvement was predominant (left to right ratio = 9: 3). All patients had bronchopleural fistula, and all were cured. The average numbers of previous thoracotomy were 5.4. The ipsilateral DALT flaps were harvested with primary closure of donor site.Results. At a mean follow-up of 1 year, no recurrence was noted. All flaps survived well. The average hospital stay was 25.8 days. Complications after reconstruction included chrondritis, partial muscle necrosis, and wound dehiscence (1 patient each). There was no donor site morbidity.Conclusions. Free DALT flaps can be selected according to different situations during surgery as long as they meet the following requirements: (1) tissue of sufficient volume and good blood supply, and (2) closure of the bronchial leak. Based on this retrospective study, use of free DALT flaps with technical refinement is a reliable method for treatment of chronic intractable empyema combined with bronchopleural fistula. [Copyright &y& Elsevier]

Spontaneous intramural esophageal hematoma is a rare cause of chest pain. Erroneous diagnosis may cause inappropriate management and disaster. We describe one case of spontaneous intramural hematoma that was successfully managed by conservative treatment. Endoscopic and radiographic images are reviewed. The benefit of endoscopic ultrasound is emphasized. [Copyright &y& Elsevier]

In this research, a novel polysaccharide (PCP) was extracted from Pleurotus citrinopileatus and purified by Sephadex G-150 gel column, and its antitumor activity was investigated using the model H22 tumor-bearing mice. PCP was found to be composed of arabinose, galactose, glucose, xylose, mannose and glucuronic acid in a proportion of 0.66: 14.59: 10.77: 1: 0.69: 0.23 with average molecular weight of 7.30 × 105 Da. Further analysis suggested that PCP was a pyranose with α-type and β-type glycosidic residues. The antitumor assays in vivo indicated that PCP could effectively suppress H22 solid tumor growth, protect immune organs and improve inflammation and anemia. Besides, Annexin V-FITC/PI double staining and JC-1 staining demonstrated that PCP could induce apoptosis of H22 hepatoma cells. The PI staining assay revealed that PCP induced H22 hepatoma cells apoptosis by arresting cell cycle in S phase. These results suggest that the polysaccharide from Pleurotus citrinopileatus possesses potential value in the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

In the present study, a polysaccharide fraction (PTP) was isolated and purified from the tubers of Pinellia ternata. We researched its structure and anti-tumor activity, and further studied its molecular mechanism of inducing apoptosis of Hep G2 cells. The results indicated that PTP was an acid heteropolysaccharide and the average molecular weight of PTP identified by HPGPC was 3.06 × 106 Da. Ion chromatography (IC) determined that PTP was mainly composed of Ara:Gal:Glu:Man:GlcA:GalA in a molar ratio of 6.98:16.56:7.25:2.04:1:4.16. Combined with the results of FT-IR and NMR spectroscopy, it was found that PTP is a pyranose containing α-configuration and β-configuration, mainly consist of β-D-Gal, α-D-Glu, α-D-Ara and β-D-Man. By analyzing the results of MTT, cell cycle, Annexin V-FITC/PI double staining and cell morphology observation, we concluded that PTP induced dose-dependent apoptosis of Hep G2 cells via S phase arrest. In addition, mitochondrial membrane potential detection and Western blot further indicated that PTP was capable of inducing apoptosis in Hep G2 cells through an endogenous mitochondria-mediated apoptotic pathway. [ABSTRACT FROM AUTHOR]

Abstract Most ectotherms are able to increase their tolerance to heat stress via the acclimation response. However, there is ongoing debate about whether the acclimation response is associated with fitness costs, and what factors can affect the consequences of acclimation are still unclear. To elucidate this, we sought to determine whether fitness costs varied with acclimation conditions in two cereal aphids, Sitobion avenae and Rhopalosiphum padi. Thus, the basal and inducible thermal tolerances (maximum critical temperature [CT max ]) and fitness traits (proportion of adult emergence, adult longevity, fecundity, and population parameters) of adult aphids were measured under three conditions of developmental acclimation: 1) 22 °C constant temperature (no acclimation), 2) 22 °C + 34 °C for 2 h per day (low daytime temperature), and 3) 22 °C + 38 °C for 2 h per day (high daytime temperature). We found that the thermal tolerances of both species were significantly higher following developmental acclimations, where higher basal and inducible thermal tolerances were observed in R. padi than in S. avenae. Low daytime temperature acclimation conditions (34 °C) resulted in negligible reproductive costs and improved the intrinsic rates of population increase in both species. In contrast, substantial fitness costs were detected in both species in response to high daytime temperature acclimation (38 °C), especially for S. avenae. Our results indicate that the effects of acclimation conditions on fitness costs differ between the two aphid species. These findings will not only enhance our understanding of species dynamics in the context of climate change but could also potentially improve pest control efforts. Highlights • Thermal tolerance of Rhopalosiphum padi and Sitobion avenae significantly increased following developmental acclimation. • R. padi had higher basal and inducible tolerances than S. avenae. • Low daytime temperature condition (34°C) resulted in negligible reproductive costs and improved the r m in both species. • High daytime temperature acclimation (38°C) accrued substantial fitness costs in both species, especially for S. avenae. [ABSTRACT FROM AUTHOR]

Iodine is an essential trace element for human health. Its deficiency in biogeochemical environment affects about two billion people worldwide. Besides universal salt iodization, the biofortification of crops with iodine has been proposed as a strategy for improving human nutrition. This study aims at exploring the effects of iodine biofortification on the fruit quality of the pepper plants. The contents of iodine, ascorbic acid, soluble sugar and total acidity of the pepper fruits grown in solution at various iodide concentration levels were measured. Furthermore, in order to reveal the mechanism of fruit quality change, the variations in Chl-a, malondialdehyde (MDA), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) of the pepper leaves at various growth periods in response to various iodine treatments were determined. The results indicated that the iodine content of the pepper fruits grown in 0.25–5.0 mg L −1 KI solutions can amount to 350–1330 μg kg −1 FW, matching the 150 μg d −1 dietary iodine allowance recommended by WHO. Thus, the pepper can be used as a candidate crop for iodine biofortification. In addition, low-moderate levels (0.25–1.0 mg L −1 ) of iodine application improved the fruit quality by enhancing the ascorbic acid and soluble sugar contents, and by reducing the total acidity of pepper fruits as well. Generally, after iodine treatments, the Chl-a concentration, and CAT, POD, SOD activities of the pepper leaves increased, while the MDA concentration decreased. The changes in photosynthetic and antioxidant capacities of the plants promoted the improvement of the pepper fruit quality. [ABSTRACT FROM AUTHOR]

Summary: Fungal infections develop slowly in immunocompetent patients and rarely a severe disease, however, they progress rapidly and usually prove fatal in immunocompromised patients. Early diagnosis and treatment of fungal infections is essential to survival of immunocompromised patients. We report a 33-year-old woman with systemic lupus erythematosus undergoing immunotherapy infected with combined invasive pulmonary aspergillosis and pulmonary cryptococcosis diagnosed by video-assisted thoracic surgery lung biopsy and she was successfully treated as a result of early diagnosis and treatment. [Copyright &y& Elsevier]

Effects of pre-damage by 500 keV argon ion implantation on deuterium-induced blistering in tungsten has been investigated. After low-energy (40 eV) and high-flux (∼10 24 D/m 2 s) deuterium plasma exposure with short exposure duration (100 s), a large increase of deuterium retention is found in the pre-damaged tungsten, while surface blistering is significantly suppressed as compared to the un-damaged one. According to elastic recoil detection analysis, a local deuterium concentration peak is observed at a depth of ∼100 nm for the un-damaged tungsten, which is supposed to be related to the surface blistering with nanometer size. Comparison of deuterium retention in the near surface (within 300 nm) and in the bulk suggests that deuterium inward diffusion is more significant in the pre-damaged tungsten. It is speculated that the creation of deuterium trap-sites and enhancement of deuterium inward diffusion give rise to an increase of critical deuterium concentration for blistering and contribute to the suppressed deuterium-induced blistering on pre-damaged tungsten under the present exposure conditions. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) gene mutations are strongly associated with lung adenocarcinoma and favorable response to EGFR tyrosine kinase inhibitor. The mutated EGFR proteins (EGFRs) are hyper-phosphorylated and refractory to receptor down-regulation. To address the discrepancy between hyper-phosphorylation and lack of down-regulation of mutant EGFRs, we have examined the expression of EGFR negative regulators in non-small cell lung cancer (NSCLC) cell lines. We found that NSCLC cell lines expressing mutant EGFRs often had low expression of various negative regulators for EGFR. Among them, tumor suppressor CD82 was up-regulated by wild type (WT) EGFR but down-regulated by mutant EGFRs. Reconstitution of CD82 exerted stronger suppressive effects on mutant EGFRs than on WT EGFR. Active exportation of CD82 through the exosome was one of the mechanisms involved in achieving the overall CD82 down-regulation in mutant EGFR-expressing lung cancer cell lines. Over-expression of mutant EGFR protein frequently occurred in the lung cancer tissues of mutant EGFR-transgenic mice and also associated with CD82 down-regulation. Immunoblot analyses on the tumor tissues from 23 lung adenocarcinoma patients (12 with WT EGFR, and 11 with mutant EGFRs) also identified significantly stronger down-regulation of CD82 in tumors with mutant EGFRs than WT. Our data indicate that CD82 down-regulation could be a critical step involved in the EGFR over-expression and the stronger tumorigenic activity triggered by EGFR mutations. Up-regulation of the CD82 level may become a promising new treatment strategy for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract: Riccardin D is a macrocyclic bisbibenzyl compound extracted from liverwort plant Dumortiera hirsuta. Our previous study showed that riccardin D induced apoptosis of human leukemia cells by targeting DNA topoisomerase II (topo II). Riccardin D has been considered as a novel DNA topo II inhibitor and potential chemotherapeutic agent for treatment of cancers. In this study, we evaluated the inhibitory effects of riccardin D on growth of human non-small cell lung cancer (NSCLC) both in vitro and in vivo. Riccardin D effectively inhibited the proliferation of NSCLC cells as estimated by the MTT assay. Further examination showed that the ability of invasion and migration of NSCLC cells was suppressed on exposure to riccardin D as estimated by the assays of scratch and transwell chamber. The anticancer activity of riccardin D was verified in mice bearing human NSCLC H460 xenografts. Riccardin D injection produced a 44.5% inhibition of cancer growth without apparent signs of toxicity to animals. Further, riccardin D induced apoptosis of NSCLC cells as evidenced by the increases of cells with externalization of phosphatidylserine and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive in H460 xenografts. The analysis of apoptotic proteins showed that riccardin D activated the caspases cascade signaling pathway as demonstrated by the increases of cleaved caspase-3 and cleaved PARP in NSCLC cells in vitro and in H460 xenografts in mice. The pBR322 DNA relaxation assay indicated that riccardin D inhibited the activity of DNA topo II in H460 and A549 cells, suggesting the mechanism of riccardin D in induction of NSCLC apoptosis. In addition, we studied the activity and expression of matrix metalloproteinases (MMPs) in NSCLC cells. The activities of MMP-2 and MMP-9 in supernatants of NSCLC cells were suppressed on exposure to riccardin D as estimated by gelatin zymography assay. The inhibitory effects of riccardin D on expressions of MMP-2 and MMP-9 were verified in H460 xenografts in mice and the decreases of vascular endothelial growth factor (VEGF) and Erk1/2 might associate with the inhibition of MMPs and NSCLC growth. Together, our results suggest that riccardin D has a high inhibitory effect on human NSCLC growth through induction of apoptosis. [Copyright &y& Elsevier]

Abstract: Riccardin D is a novel macrocyclic bisbibenzyl compound extracted from Chinese liverwort plant Dumortiera hirsuta. Our previous studies showed that riccardin D is a DNA topo II inhibitor and has therapeutic potential for treatment of cancers. In this combined in vitro and in vivo study, we examined the inhibitory effects of riccardin D on tumor angiogenesis and the subsequent effect of anticancer activity was evaluated. Incubation with riccardin D weakly inhibited the proliferation of human umbilical vascular endothelial cells (HUVEC) as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT) assay. The scratch wound experiment showed that riccardin D effectively decreased the motility and migration of HUVEC cells. Riccardin D inhibited the formation of capillary tube as demonstrated by decrease of branch points formed by HUVEC cells on 3-D Matrigel. We examined the levels of angiogenic factors including vascular endothelial growth factor (VEGF), VEGF receptor 2, epidermal growth factor receptor (EGF receptor), and matrix metalloproteinase (MMPs) in HUVEC cells. The expressions of VEGF, phospho-VEGF receptor 2, EGF receptor and MMP-2 were significantly reduced by riccardin D as estimated by Western blot assay and real-time quantitative PCR analysis. The decrease of VEGF was also detected in riccardin D-treated human lung cancer H460 cells. The anticancer activity of riccardin D was then evaluated in a mouse model in which riccardin D delayed the growth of H460 xenografts without obvious toxicity to animals after three weeks injection. To evaluate the role of antiangiogenesis of riccardin D in mice, CD34 immunohistochemical staining was employed to analyze the mean vascular density in H460 xenograft tissues. The number of blood vessels was significantly decreased after riccardin D treatment. These results suggest that riccardin D display the inhibitory effect on growth of human lung carcinoma cells and that the inhibition of angiogenesis may involve in anticancer activity of riccardin D. [Copyright &y& Elsevier]

Summary: Mutational analysis was performed in the kinase domain (exons 18–21) of the EGFR gene on tumor tissues of 65 non-small cell lung cancer (NSCLC) patients who had received gefitinib monotherapy. The association between EGFR gene mutation, gefitinib treatment response, and the overall survival were evaluated. In total, EGFR mutations with complex patterns were identified in 32 tumors. The overall mutation rate was 49.2% (32/65). Twenty of the 32 patients were responders, 10 non-responders, and 2 not assessable. The most common mutation in non-responders was L858R. Gefitinib responsiveness was only significantly associated with EGFR mutation and adenocarcinoma. The median survival for responder (15.5 months) was much longer than non-responder (9.23 months), though the difference only had marginal significance (p =0.056). The difference of overall survival between patients with and without EGFR mutation was non-significant (p =0.7819), mainly due to the short survival of the non-responders with EGFR mutations (median survival=6.2 months). Our study revealed that the response to gefitinib treatment in NSCLC patients with EGFR mutations could be quite variable even for the same EGFR mutation type. An analysis of the various EGFR mutations and the response patterns was also performed and compared with recently published reports on EGFR mutation and gefitinib responsiveness. [Copyright &y& Elsevier]

Summary: Background: The use of a vancomycin dosing nomogram is an alternative and more cost-effective method to conventional dosing; it reliably allows the achievement of trough vancomycin serum concentrations of 5–15mg/l, with a successful clinical response. Recent guidelines have further recommended that the trough concentration be maintained at 15–20mg/l for complicated infections. However, to date no published nomogram has been constructed to achieve the optimal trough of 15–20mg/l in an Asian population. This study aimed to develop two vancomycin nomograms for the achievement of trough concentrations of 5–15mg/l and 15–20mg/l in the Taiwanese population, and to ensure the clinical efficacy and safety of such nomograms. Methods: The estimated concentrations and the real concentrations in our patient population were compared between six pharmacokinetic models to see which was the most precise. As the Ambrose method was the best at predicting the trough, this was used to create two nomograms, one for a target trough at 5–15mg/l and the other for a target trough at 15–20mg/l. We then evaluated the nomograms by analyzing the number of patients with the target vancomycin trough concentration, clinical and microbiological outcomes, and safety. Results: More patients who had dosing according to the nomogram had a vancomycin trough concentration within the desired target range than patients who had conventional dosing (65.1% vs. 32.1%, p = 0.001). These patients also had a higher rate of ‘cure’ as the clinical response (35.7% vs. 27.1%) and ‘eradication’ as the microbiological response (46.4% vs. 29.2%), and a lower rate of nephrotoxicity (14.3% vs. 22.9%). For the patients with a complicated infection, more had a trough between 15 and 20mg/l when vancomycin was dosed with the nomogram than when dosed conventionally (41.2% vs. 12.1%, p = 0.019). Conclusions: We found that when dosing vancomycin with these nomograms, patients tended to have vancomycin trough concentrations within the target range and also to have a better outcome with regard to clinical efficacy and the safety profile. [Copyright &y& Elsevier]