BACKGROUND: Various methods based on gold nanoparticles (AuNPs) have been applied to enhance the photothermal effect. Among these methods, combining gold nanoparticles and stem cells has been suggested as a new technique for elevating the efficiency of photothermal therapy (PT) in terms of enhancing tumor targeting effect. However, to elicit the efficiency of PT using gold nanoparticles and stem cells, delivering large amounts of AuNPs into stem cells without loss should be considered. METHODS: AuNPs, AuNPs-decorated silica nanoparticles, and silica-capped and AuNPs-decorated silica nanoparticles (SGSs) were synthesized and used to treat human mesenchymal stem cells (hMSCs). After evaluating physical properties of each nanoparticle, the concentration of each nanoparticle was estimated based on its cytotoxicity to hMSCs. The amount of AuNPs loss from each nanoparticle by exogenous physical stress was evaluated after exposing particles to a gentle shaking. After these experiments, in vitro and in vivo photothermal effects were then evaluated. RESULTS: SGS showed no cytotoxicity when it was used to treat hMSCs at concentration up to 20 lg/mL. After intravenous injection to tumor-bearing mice, SGS-laden hMSCs group showed significantly higher heat generation than other groups following laser irradiation. Furthermore, in vivo photothermal effect in the hMSC-SGS group was significantly enhanced than those in other groups in terms of tumor volume decrement and histological outcome. CONCLUSION Our results suggest that additional silica layer in SGSs could protect AuNPs from physical stress induced AuNPs loss. The strategy applied in SGS may offer a prospective method to improve PT.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

OBJECTIVE: This study aimed to assess the anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Eighty-seven adult patients with various hematologic diseases, who were scheduled to receive autologous or allogeneic HSCT, were enrolled. The M.D. Anderson Symptom Inventory and the Hospital Anxiety Depression Scale were applied prospectively at hospital admission (D-14), on the day of transplantation (D day), and at 7 (D7) and 14 days (D14) after transplantation. RESULTS: The severity of both anxiety and depressive symptoms increased over time, with a peak at D7, and then showed a downturn at D14. Physical distresses also started with mild intensity at base line, which were continuously aggravated until D7, and then a partial recovery afterwards. Approximately, 52% of the participants had significantly high anxiety or depression before the start of HSCT. The occurrence of aggravation of pain, nausea, shortness of breath, and lack of appetite was associated with the development of anxiety during isolation period. The patients with significant baseline anxiety had higher scores on fatigue and shortness of breath items at D7 compared to those without. CONCLUSION: Our finding suggests the importance of psychiatric approaches, including preventive measures, for the patients undergoing HSCT.
Adult ; Anxiety ; Appetite ; Depression ; Dyspnea ; Fatigue ; Hematologic Diseases ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Hospitalization ; Humans ; Nausea ; Prospective Studies

OBJECTIVES: The aim of this study was to compare the osteogenic effects of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbit calvarial defects with DDM and anorganic bovine bone (ABB) combined with rhBMP-2. MATERIALS AND METHODS: Four round defects with 8-mm diameters were created in each rabbit calvaria. Each defect was treated with one of the following: 1) DDM, 2) ABB/rhBMP-2, or 3) DDM/rhBMP-2. The rhBMP-2 was combined with DDM and ABB according to a stepwise dry and dip lyophilizing protocol. Histological and microcomputed tomography (µCT) analyses were performed to measure the amount of bone formation and bone volume after 2- and 8-week healing intervals. RESULTS: Upon histological observation at two weeks, the DDM and ABB/rhBMP-2 groups showed osteoconductive bone formation, while the DDM/rhBMP-2 group showed osteoconductive and osteoinductive bone formation. New bone formation was higher in DDM/rhBMP-2, DDM and ABB decreasing order. The amounts of bone formation were very similar at two weeks; however, at eight weeks, the DDM/rhBMP-2 group showed a two-fold greater amount of bone formation compared to the DDM and ABB/rhBMP-2 groups. The µCT analysis showed markedly increased bone volume in the DDM/rhBMP-2 group at eight weeks compared with that of the DDM group. Notably, there was a slight decrease in bone volume in the ABB/rhBMP-2 group at eight weeks. There were no significant differences among the DDM, ABB/rhBMP-2, and DDM/rhBMP-2 groups at two or eight weeks. CONCLUSION: Within the limitations of this study, DDM appears to be a suitable carrier for rhBMP-2 in orthotopic sites.
Dentin* ; Humans* ; Osteogenesis ; Skull ; X-Ray Microtomography

We herein describe a 70-year-old woman who presented with respiratory failure due to extensive lung adenocarcinoma. Despite advanced disease, care in the intensive care unit with ventilator support was performed because she was a newly diagnosed patient and was considered to have the potential to recover after cancer treatment. Because prompt control of the cancer was needed to treat the respiratory failure, empirical treatment with an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was initiated before confirmation of EGFR-mutant adenocarcinoma, and the patient was successfully treated. Later, EGFR-mutant adenocarcinoma was confirmed.
Adenocarcinoma* ; Aged ; Female ; Humans ; Intensive Care Units ; Lung* ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Respiration, Artificial ; Respiratory Insufficiency* ; Ventilators, Mechanical ; Erlotinib Hydrochloride

We herein describe a 70-year-old woman who presented with respiratory failure due to extensive lung adenocarcinoma. Despite advanced disease, care in the intensive care unit with ventilator support was performed because she was a newly diagnosed patient and was considered to have the potential to recover after cancer treatment. Because prompt control of the cancer was needed to treat the respiratory failure, empirical treatment with an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was initiated before confirmation of EGFR-mutant adenocarcinoma, and the patient was successfully treated. Later, EGFR-mutant adenocarcinoma was confirmed.
Adenocarcinoma ; Aged ; Female ; Humans ; Intensive Care Units ; Lung ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Respiration, Artificial ; Respiratory Insufficiency ; Ventilators, Mechanical ; Erlotinib Hydrochloride

BACKGROUND/AIMS: While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea. METHODS: The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0+/-11.0 years, mean+/-SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated. RESULTS: The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001). CONCLUSIONS: The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Endoscopy ; Esophageal and Gastric Varices/*diagnosis/mortality/therapy ; Female ; *Gastrointestinal Hemorrhage ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prognosis ; Republic of Korea ; Retrospective Studies ; Sclerotherapy ; Severity of Illness Index ; Treatment Outcome ; Young Adult

BACKGROUND: Inflammatory cytokines play an important role in human immune responses to malaria, although the role of these mediators in pathogenesis is unclear. In this study, we evaluated changes in cytokine levels following chemotherapy, and determined whether cytokine levels in serum correlated with the hematological parameters in the Korean vivax malarial patients. METHODS: The study population was composed of 31 patients in Inje University Ilsan Paik Hospital who were diagnosed with Plasmodium vivax infection. Cytokine profiles, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 levels, were assessed in serum samples obtained from the malaria patients three times, at the time of diagnosis (stage I) and after treatment with hydroxychloroquine (stage II) and primaquine (stage III). The level of each cytokine was measured using commercially available serum-based ELISA kits. Hematological parameters were simultaneously measured using a hematology autoanalyzer. RESULTS: At thetime of diagnosis, the TNF-alpha (mean, 62.9 pg/mL), IL-6 (mean, 45.5 pg/mL), and IL-10 (mean, 237.7 pg/mL) levels in the malaria patients were higher than the reference values. After treatment with hydroxychloroquine, these levels (TNF-alpha, P<0.01; IL-6, P<0.05; IL-10, P<0.01) significantly decreased to near-normal levels. Significant positive correlations were observed among the cytokine levels, but not between the cytokine levels and other hematological parameters. CONCLUSIONS: In this study, TNF-alpha, IL-6, and IL-10 levels increased at the time of diagnosis and rapidly decreased to normal levels after treatment the levels of these cytokines did not correlate with other hematological parameters.
Cytokines ; Enzyme-Linked Immunosorbent Assay ; Hematology ; Humans ; Hydroxychloroquine ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Malaria ; Malaria, Vivax ; Plasmodium vivax ; Primaquine ; Reference Values ; Tumor Necrosis Factor-alpha

BACKGROUNDS/AIMS: The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. METHODS: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-beta (TGF-beta) were measured by reverse transcriptase-polymerase chain reaction. RESULTS: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean+/-SD) were 0, 1.3+/-0.5, 2.6+/-0.5, and 3.4+/-0.5, respectively (P<0.05), serum HA levels were 12.5+/-3.2, 30.0+/-4.3, 228.6+/-157.7, and 391.3+/-207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4+/-2.8, 17.6+/-3.8, 17.9+/-2.4, and 33.4+/-3.4 microgram/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-beta1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-beta1, and histomorphological grade of hepatic fibrosis (P<0.001). CONCLUSIONS: These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis.
Animals ; Bile Ducts/pathology/surgery ; Biological Markers/blood ; Collagen/analysis/genetics ; Hyaluronic Acid/*blood ; Hydroxyproline/blood ; Ligation ; Liver/metabolism/*pathology ; Liver Cirrhosis, Experimental/*diagnosis/metabolism/pathology ; Male ; Models, Animal ; Procollagen/analysis/genetics ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; Sickness Impact Profile ; Transforming Growth Factor beta/analysis/genetics